What are the recommended diagnostic labs for Myasthenia Gravis (MG)?

Diagnostic Labs for Myasthenia Gravis (MG)

The recommended diagnostic workup for myasthenia gravis should include acetylcholine receptor (AChR) antibodies, anti-striated muscle antibodies, and if AChR antibodies are negative, muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies. 1

Primary Serological Testing

• AChR antibodies: First-line test

  • Present in 50% of ocular MG and 80% of generalized MG 2
  • Testing methods:
    • Radioimmunoprecipitation assay (RIPA): Traditional method with nearly 100% specificity but sensitivity of 50-92% 2
    • Cell-based assays (CBAs): Higher sensitivity than RIPA, especially for detecting clustered AChR antibodies in RIPA-negative patients 3

• If AChR antibodies negative:

  • MuSK antibodies: Present in 5-8% of MG patients 4
  • LRP4 antibodies: Present in 2-50% of seronegative cases 2

Recommended Testing Algorithm

1. Start with binding and blocking assays for AChR antibodies using RIPA and/or fixed cell-based assay (f-CBA) 2
2. If AChR antibody negative, reflex to MuSK antibody testing using RIPA and/or CBAs 2
3. If both AChR and MuSK antibodies are negative, consider clustered live cell-based assay (L-CBA) 2
   • CBA can detect antibodies in 38.1% of RIPA-negative MG patients with 100% specificity 3

Additional Diagnostic Tests

• Electrodiagnostic studies 1:

  • Neuromuscular junction testing with repetitive stimulation (shows decremental response)
  • Single-fiber EMG (shows increased jitter) - considered gold standard with >90% sensitivity for ocular MG 5
  • Nerve conduction studies to exclude neuropathy

• Pulmonary function assessment 1:

  • Negative inspiratory force
  • Vital capacity

• Laboratory tests for concurrent conditions 1:

  • Creatine phosphokinase (CPK)
  • Aldolase
  • ESR and CRP (to evaluate for possible concurrent myositis)

• Other diagnostic tests:

  • Ice pack test: Highly specific for MG 5
  • Edrophonium (Tensilon) test: 95% sensitive for generalized MG and 86% sensitive for ocular MG 5, 6
    • Intravenous dosage (adults): 0.2 mL (2 mg) initially, followed by remaining 0.8 mL (8 mg) if no reaction occurs after 45 seconds 6
    • Caution: Carries risks including bradycardia, bronchospasm, and hypotension 5

• Imaging:

  • MRI of brain and/or spine to rule out CNS involvement 1
  • Chest imaging to evaluate for thymoma (present in 10-20% of AChR MG patients) 4

• Cardiac evaluation if respiratory insufficiency or elevated CPK/troponin T 1:

  • ECG
  • Transthoracic echocardiogram (TTE) for possible concomitant myocarditis

Clinical Pearls

• Approximately 10% of MG patients are seronegative for known antibodies 4
• Consider neurology consultation as part of the diagnostic process 1
• CBAs are particularly useful in diagnosing RIPA-negative MG in children 3
• Patients with antibodies only to clustered AChRs tend to be younger with milder disease 3
• Different serologic MG classes show important differences in clinical presentation, treatment responsiveness, and disease mechanisms 4

Common Pitfalls to Avoid

• Relying solely on RIPA for antibody detection may miss cases detectable by CBA
• Failing to consider MG in patients with fluctuating muscle weakness, especially ocular symptoms
• Not testing for all relevant antibodies (AChR, MuSK, LRP4) in suspected cases
• Overlooking the possibility of thymoma in adult patients with MG