What is the patient workup for myasthenia gravis?

Patient Workup for Myasthenia Gravis

Begin with serologic testing for acetylcholine receptor (AChR) antibodies and antistriated muscle antibodies, followed by electrodiagnostic studies if antibodies are negative or clinical suspicion remains high. 1

Clinical Assessment

Look for these specific features during history and physical examination:

• Fatigable or fluctuating muscle weakness that worsens with repeated muscle use and improves with rest, typically more proximal than distal 2, 1
• Ocular involvement: ptosis and extraocular movement abnormalities (diplopia) - present in approximately 50% of initial presentations 2
• Bulbar symptoms: dysphagia, dysarthria, facial muscle weakness, and drooling 2
• Generalized limb weakness: difficulty climbing stairs, proximal muscle weakness 2
• Respiratory symptoms: shortness of breath with light activity, which requires immediate attention 2
• Pupils are characteristically NOT affected - pupillary involvement should immediately redirect you toward third nerve palsy or other diagnoses 2

Bedside Testing

Perform the ice pack test for patients with ptosis:

• Apply an ice pack over closed eyes for 2 minutes 2
• This test is highly specific for myasthenia gravis if ptosis improves 2, 1
• Particularly useful for ocular symptoms 2

Assess respiratory function immediately:

• Measure negative inspiratory force (NIF) and vital capacity (VC) 3
• Apply the "20/30/40 rule" to identify patients at risk of respiratory failure: vital capacity <20 ml/kg, maximum inspiratory pressure <30 cmH₂O, or maximum expiratory pressure <40 cmH₂O 3
• Perform single breath count test: patient takes deep breath and counts at rate of two numbers per second while exhaling; counting to ≥25 correlates with normal respiratory muscle function 3

Laboratory Testing

First-line serologic testing:

• AChR antibodies - positive in 80-85% of generalized MG, but only 40-77% of ocular MG 2, 1
• Antistriated muscle antibodies 3, 1

If AChR antibodies are negative:

• Test for muscle-specific kinase (MuSK) antibodies 3, 1
• Test for lipoprotein-related protein 4 (LRP4) antibodies 3, 1

Additional laboratory studies:

• CPK, aldolase, ESR, and CRP to evaluate for concurrent myositis 3
• Troponin to evaluate myocardial involvement 4

Electrodiagnostic Studies

Perform if antibodies are negative or clinical suspicion remains high:

• Repetitive nerve stimulation studies 2
• Single-fiber EMG - has >90% sensitivity for ocular myasthenia 2
• Note that standard EMG and nerve conduction studies may be normal early in disease course 2

Cardiac Evaluation

If respiratory insufficiency or elevated CPK/troponin:

• ECG 3
• Transthoracic echocardiogram to rule out concurrent myocarditis 3
• Consider cardiac MRI 4

Imaging Studies

Chest imaging for thymoma evaluation:

• Any patient with suspected myasthenia gravis requiring surgery must have serum anti-AChR antibody levels measured preoperatively 2
• Approximately 30-50% of patients with thymomas have myasthenia gravis 2

Brain/orbital imaging when indicated:

• Brain imaging may help exclude brainstem strokes that can mimic myasthenia gravis 2
• Orbital CT/MRI to differentiate thyroid eye disease (tendon-sparing muscle enlargement) from myasthenia 2

Critical Differential Diagnoses to Exclude

Third nerve palsy:

• Distinguished by pupillary abnormalities (pupils are spared in MG) 2
• Requires immediate neuroimaging and vascular workup given risk of aneurysm or ischemia 2

Thyroid eye disease:

• Causes restrictive myopathy with mechanical limitation rather than neuromuscular junction dysfunction 2
• Key features: proptosis, eyelid retraction, fixation on forced duction testing 2
• Orbital imaging shows tendon-sparing muscle enlargement 2

Botulism:

• Differentiated by symmetric cranial nerve palsies and gastrointestinal symptoms 2

Guillain-Barré syndrome:

• CSF protein is often elevated by week 2 (CSF is typically normal in MG) 2

Medication Review - Critical Safety Step

Immediately identify and discontinue these medications that can worsen myasthenia gravis:

• β-blockers 3, 2, 1
• IV magnesium (absolutely contraindicated) 3, 1
• Fluoroquinolones 3, 2, 1
• Aminoglycosides 3, 2, 1
• Macrolide antibiotics 3, 2, 1

Common Pitfalls to Avoid

• Don't rely on a single negative test - no single test is specific for myasthenia gravis; diagnosis relies on combined results 5
• Don't miss seronegative MG - 15-23% of generalized MG patients are AChR-negative, requiring MuSK and LRP4 testing 1
• Don't underestimate ocular MG - 50-80% of patients with isolated ocular symptoms will develop generalized myasthenia within a few years 2, 1
• Don't delay respiratory assessment - respiratory insufficiency may develop without obvious dyspnea symptoms 3
• Don't assume normal pupils exclude MG - but abnormal pupils should redirect you to other diagnoses 2