How to diagnose Myasthenia Gravis?

Diagnosis of Myasthenia Gravis

The diagnosis of myasthenia gravis requires a combination of clinical evaluation, serological testing for specific antibodies, and electrodiagnostic studies, with anti-acetylcholine receptor (AChR) antibody testing being the primary diagnostic test for confirmation.

Clinical Presentation

• Fatigable or fluctuating muscle weakness, typically more proximal than distal, is the hallmark clinical presentation of myasthenia gravis 1
• Ocular symptoms (ptosis, diplopia) are common initial manifestations, with generalization to other muscle groups occurring in approximately 80% of cases 2
• Bulbar involvement may present as dysphagia, dysarthria, and facial muscle weakness 1
• Symptoms worsen with repeated use of affected muscles and improve with rest 3

Primary Diagnostic Tests

• Anti-acetylcholine receptor (AChR) antibody testing is recommended as the first-line diagnostic test, with positive results in approximately 80% of patients with generalized myasthenia gravis but only about 50% of patients with purely ocular myasthenia 4
• Anti-muscle-specific kinase (MuSK) antibody testing should be performed when AChR antibodies are negative, as approximately one-third of seronegative patients will be positive for anti-MuSK antibodies 4
• Single-fiber electromyography (SFEMG) is considered the gold standard diagnostic test with over 90% sensitivity, particularly valuable for ocular myasthenia gravis 4
• Repetitive nerve stimulation testing has lower sensitivity than SFEMG, being positive in only about one-third of patients with ocular myasthenia 4

Bedside Diagnostic Tests

• The ice pack test is highly specific and involves applying an ice pack over closed eyes for 2 minutes to evaluate for improvement in ptosis 4, 1
• The edrophonium (Tensilon) test should be performed in a monitored setting with atropine available due to potential muscarinic side effects 4
  • For adults: 2 mg IV initially, followed by remaining 8 mg if no reaction occurs after 45 seconds 5
  • A positive test shows increased muscle strength in untreated myasthenics 5
  • The test has 95% sensitivity for generalized myasthenia and 86% sensitivity for ocular myasthenia 4

Additional Diagnostic Evaluations

• Pulmonary function assessment, including negative inspiratory force and vital capacity measurements, is crucial to evaluate respiratory muscle involvement 4, 1
• Laboratory tests for possible concurrent conditions:
  • Creatine phosphokinase (CPK), aldolase, ESR, and CRP to evaluate for possible concurrent myositis 4
  • Cardiac evaluation (ECG, echocardiogram) if respiratory insufficiency or elevated CPK/troponin T is present 4
• MRI of brain and/or spine may be needed to rule out alternative diagnoses depending on symptoms 4

Diagnostic Algorithm

1. Clinical evaluation for fatigable weakness
2. Serological testing:
   • Anti-AChR antibodies (first)
   • If negative, test for anti-MuSK antibodies
3. Electrodiagnostic studies:
   • Single-fiber EMG (most sensitive)
   • Repetitive nerve stimulation
4. Bedside tests:
   • Ice pack test
   • Edrophonium (Tensilon) test in monitored setting

Important Considerations and Pitfalls

• Avoid medications that can exacerbate myasthenia symptoms during testing, including β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolides 4, 1
• Myasthenic crisis must be distinguished from cholinergic crisis, as management differs significantly 5
• False-negative antibody tests can occur, particularly in purely ocular myasthenia, making clinical evaluation and electrodiagnostic studies essential 4, 2
• Myasthenia gravis can be associated with thymoma in approximately 20% of patients and with other autoimmune diseases such as hyperthyroidism and Hashimoto's disease 2

Response Patterns to Edrophonium Testing

• Myasthenic response: Increased muscle strength (diagnostic in untreated patients) 5
• Adequate response: No change in muscle strength (seen in treated patients with stabilized therapy) 5
• Cholinergic response: Decreased muscle strength with side effects like lacrimation, diaphoresis, salivation (indicates overtreatment) 5