How do you diagnose myasthenia gravis (MG)?

Diagnostic Testing for Myasthenia Gravis

The diagnosis of myasthenia gravis requires a combination of serologic antibody testing (acetylcholine receptor antibodies as first-line), electrodiagnostic studies (single-fiber EMG or repetitive nerve stimulation), and clinical bedside tests (ice pack test or edrophonium test), with neurology consultation recommended for all suspected cases. 1, 2

Serologic Testing (Primary Diagnostic Approach)

• Acetylcholine receptor (AChR) antibodies are the first-line blood test and confirm diagnosis in approximately 80-85% of patients with generalized myasthenia gravis, though only 50% with purely ocular disease test positive 2, 3, 4

• If AChR antibodies are negative, proceed to test for muscle-specific kinase (MuSK) antibodies, which are positive in approximately one-third of seronegative patients (5-8% overall) 1, 2, 4

• Antistriated muscle antibodies should also be obtained, particularly as they correlate with thymoma risk 1

• Lipoprotein-related protein 4 (LRP4) antibodies can be tested if both AChR and MuSK are negative, though present in <1% of patients 1, 4

Electrodiagnostic Studies (Gold Standard Confirmation)

• Single-fiber electromyography (SFEMG) is the most sensitive test with >90% sensitivity for ocular myasthenia and is considered the gold standard in many centers 3, 5

• Repetitive nerve stimulation (RNS) testing shows decremental response but is less sensitive than SFEMG, positive in only about one-third of patients with ocular myasthenia 3, 5

• Nerve conduction studies (NCS) and needle EMG should be performed to exclude neuropathy and evaluate for concurrent myositis 1

Bedside Clinical Tests

• Ice pack test: Apply ice pack over closed eyes for 2 minutes; reduction of ptosis is highly specific for myasthenia gravis, particularly for ocular symptoms 2, 3

• Edrophonium (Tensilon) test: Administer 2 mg IV initially (0.2 mL), wait 45 seconds; if no reaction, give remaining 8 mg (0.8 mL) 6, 5

  • Sensitivity is 95% for generalized myasthenia and 86% for ocular myasthenia 3
  • Must be performed in monitored setting with atropine 0.4-0.5 mg available for cholinergic side effects 1, 6
  • In children <75 lbs, use 1 mg initial dose; >75 lbs use 2 mg initial dose 6

Additional Mandatory Workup

• Pulmonary function testing with negative inspiratory force and vital capacity to assess respiratory muscle involvement 1, 2, 3

• Creatine phosphokinase (CPK), aldolase, ESR, and CRP to evaluate for possible concurrent myositis 1, 3

• CT chest with contrast after confirming diagnosis to evaluate for thymoma, which occurs in 10-20% of AChR-positive patients 3

• Cardiac evaluation with ECG and transthoracic echocardiogram if respiratory insufficiency or elevated CPK/troponin T present, to rule out concomitant myocarditis 1, 3

• MRI of brain and/or spine depending on symptoms, to rule out CNS involvement or alternative diagnoses 1, 3

Critical Medication Avoidance During Testing

Avoid medications that can exacerbate myasthenic symptoms: β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolides 1, 2, 3

Neurology Consultation

All grades of suspected myasthenia gravis warrant immediate neurology consultation given the potential for progressive disease leading to respiratory compromise 1, 2