What are the diagnostic approaches and treatment options for myasthenia gravis?

Diagnostic Approach for Myasthenia Gravis

Begin with serologic testing for anti-acetylcholine receptor (AChR) antibodies as the first-line diagnostic test, which confirms the diagnosis in approximately 80% of patients with generalized myasthenia gravis. 1, 2

Initial Clinical Assessment

Look specifically for these characteristic features:

• Fatigable or fluctuating muscle weakness that worsens with repetitive use and improves with rest, typically affecting proximal muscles more than distal 1
• Ocular symptoms including ptosis and extraocular movement abnormalities (diplopia) 1
• Bulbar involvement manifesting as dysphagia, dysarthria, facial muscle weakness, or drooling 1
• Critically important: pupils are characteristically NOT affected - the presence of pupillary abnormalities should immediately redirect you toward third nerve palsy or other etiologies rather than myasthenia gravis 1

Serologic Testing Algorithm

Step 1: Anti-AChR antibodies (first-line test)

• Present in approximately 80% of generalized MG patients 2
• Sensitivity drops to only 50% in purely ocular myasthenia 2
• This test alone confirms the diagnosis when positive 2

Step 2: Anti-MuSK antibodies (if AChR-negative)

• Approximately one-third of seronegative patients will be MuSK-positive 2
• Must be tested when AChR antibodies are negative 2

Step 3: Anti-striated muscle antibodies

• Should be included in the initial workup 1, 2

Electrodiagnostic Studies

When antibody testing is negative or additional confirmation is needed:

• Single-fiber electromyography (SFEMG) is the gold standard with >90% sensitivity for ocular myasthenia 2
• Repetitive nerve stimulation is less sensitive (positive in only one-third of ocular cases) but more widely available 2

Bedside Diagnostic Tests

Ice pack test (highly specific):

• Apply ice pack over closed eyes for 2 minutes 1, 2
• Observe for reduction in ptosis or improvement in extraocular movements 1
• Highly specific for myasthenia gravis, particularly for ocular symptoms 1, 2

Edrophonium (Tensilon) test:

• 95% sensitivity for generalized MG and 86% for ocular MG 2
• Requires experienced practitioners with atropine immediately available due to muscarinic side effects 2
• Adults: inject 0.2 mL (2 mg) IV within 15-30 seconds; if no reaction after 45 seconds, inject remaining 0.8 mL (8 mg) 3
• Children ≤75 lbs: 0.1 mL (1 mg) IV, titrate up to 0.5 mL (5 mg) in increments 3
• Children >75 lbs: 0.2 mL (2 mg) IV, titrate up to 1 mL (10 mg) 3

Essential Supplementary Workup After Diagnosis

Once MG is confirmed, immediately order:

• CT chest with contrast to evaluate for thymoma, which occurs in 10-20% of AChR-positive patients 2
• Pulmonary function testing with negative inspiratory force (NIF) and vital capacity (VC) to assess respiratory muscle involvement 2
• CPK, aldolase, ESR, and CRP to evaluate for concurrent myositis 2
• Troponin and ECG (consider echocardiogram or cardiac MRI) to rule out concomitant myocarditis 2

Critical Pitfalls to Avoid

• Do not overlook the preoperative assessment: Any patient with suspected MG requiring surgery must have serum anti-AChR antibody levels measured preoperatively to avoid respiratory failure during anesthesia 1
• Thymoma association: Approximately 30-50% of patients with thymomas have myasthenia gravis, and in approximately 20% of thymoma patients, mortality is related to MG 1
• Medication review: Immediately identify and avoid β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolide antibiotics, which can exacerbate symptoms 1, 2
• Monitor for generalization: 50-80% of patients with initial ocular symptoms develop generalized myasthenia within a few years, requiring regular respiratory function assessment 1, 2