What are the recommended laboratory tests for diagnosing Myasthenia gravis?

Laboratory Testing for Myasthenia Gravis

The recommended laboratory tests for diagnosing myasthenia gravis include anti-acetylcholine receptor antibodies, anti-muscle-specific kinase antibodies, and single-fiber electromyography, which is considered the gold standard for diagnosis in many centers. 1

Primary Diagnostic Tests

• Anti-acetylcholine receptor (AChR) antibodies - These antibodies (binding, blocking, or modulating) can confirm the diagnosis and are present in approximately 80% of patients with generalized myasthenia gravis, though only about 50% of patients with purely ocular myasthenia will test positive 1, 2

• Anti-muscle-specific kinase (MuSK) antibodies - Should be tested when AChR antibodies are negative, as approximately one-third of seronegative patients will be positive for anti-MuSK antibodies 1, 3

• Anti-lipoprotein-related protein 4 (LRP4) antibodies - A newer antibody test that can identify additional patients who are negative for both AChR and MuSK antibodies 1, 2

• Single-fiber electromyography (SFEMG) - Considered the gold standard for diagnosis in many centers, with over 90% sensitivity for ocular myasthenia gravis 1

• Repetitive nerve stimulation testing - Less sensitive than SFEMG, positive in only about one-third of patients with ocular myasthenia 1

Additional Diagnostic Tests

• Ice pack test - Application of an ice pack over closed eyes for 2 minutes (for ptosis) or 5 minutes (for strabismus) may demonstrate reduction of symptoms; highly specific for myasthenia gravis 1

• Edrophonium (Tensilon) test - Should be performed by experienced practitioners in a monitored setting with atropine available due to potential muscarinic side effects; 95% sensitive for generalized myasthenia and 86% sensitive for ocular myasthenia 1

• Anti-striated muscle antibodies - Particularly useful when thymoma is suspected, as patients with thymoma typically have higher antibody titers 1, 4

Supplementary Tests for Comprehensive Evaluation

• Pulmonary function assessment - Including negative inspiratory force and vital capacity measurements to evaluate respiratory muscle involvement 1

• Creatine phosphokinase (CPK), aldolase, ESR, and CRP - To evaluate for possible concurrent myositis 1

• Cardiac evaluation - ECG and transthoracic echocardiogram if respiratory insufficiency or elevated CPK/troponin T is present, to rule out concomitant myocarditis 1

• MRI of brain and/or spine - Depending on symptoms, to rule out CNS involvement or alternative diagnoses 1

Testing Algorithm

1. Initial serological testing:

   • Anti-AChR antibodies (binding, blocking, modulating)
   • If negative, proceed to anti-MuSK and anti-LRP4 antibodies 1, 3

2. Electrophysiological testing:

   • Single-fiber EMG (preferred)
   • Repetitive nerve stimulation 1

3. Clinical confirmation tests:

   • Ice pack test
   • Edrophonium (Tensilon) test (when appropriate facilities available) 1

Important Considerations and Pitfalls

• Approximately 10% of myasthenia gravis patients remain seronegative despite comprehensive antibody testing 2

• Cell-based assays (CBAs) may detect antibodies in previously seronegative patients and should be considered when conventional tests are negative 3

• The antibody profile can help predict clinical manifestations, prognosis, and response to treatment, making accurate serological testing essential for personalized therapeutic approaches 3, 2

• Avoid medications that can exacerbate myasthenia symptoms during testing, including β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolides 1

• Patients with purely ocular symptoms typically have lower antibody titers, which may lead to false-negative results 4

• Testing should be performed before initiating immunosuppressive therapy when possible, as treatment may affect antibody levels 5