What is the recommended workup and treatment for a patient with new onset myasthenia gravis (MG)?

Workup for New Onset 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

Initial Clinical Assessment

Evaluate for the characteristic presentation of fatigable muscle weakness that worsens with repeated use and improves with rest 1:

• Ocular symptoms: Ptosis and diplopia (present in ~50% of initial presentations), with characteristically normal pupils 1
• Bulbar symptoms: Dysphagia, dysarthria, facial weakness, and drooling 1
• Limb weakness: Proximal > distal pattern, difficulty climbing stairs 1
• Respiratory symptoms: Shortness of breath with light activity (requires immediate attention) 1

Bedside Testing

• Ice pack test: Highly specific if ptosis improves after ice application, particularly useful for ocular symptoms 1
• Respiratory function assessment: Measure negative inspiratory force (NIF) and vital capacity (VC) immediately 2, 1
  • Apply the "20/30/40 rule" to identify respiratory failure risk: VC <20 ml/kg, maximum inspiratory pressure <30 cmH₂O, or maximum expiratory pressure <40 cmH₂O 1
  • Single breath count test: Counting to ≥25 correlates with normal respiratory function 1

Laboratory Workup

First-line serologic testing 2, 1:

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

If AChR antibodies are negative 2, 1:

• Muscle-specific kinase (MuSK) antibodies 2, 1
• Lipoprotein-related protein 4 (LRP4) antibodies 2, 1

Additional laboratory studies 2:

• CPK, aldolase, ESR, CRP (to evaluate for concurrent myositis) 2
• Troponin T (if respiratory insufficiency or elevated CPK present) 2

Electrodiagnostic Studies

• Repetitive nerve stimulation and single-fiber EMG (>90% sensitivity for ocular myasthenia) 1
• Perform neuromuscular junction testing with repetitive stimulation and/or jitter studies 2
• Nerve conduction study (NCS) to exclude neuropathy 2
• Needle EMG to evaluate for myositis 2

Cardiac Evaluation

If respiratory insufficiency or elevated CPK/troponin 2, 1:

• ECG and transthoracic echocardiogram (TTE) to rule out concurrent myocarditis 2, 1
• Consider cardiac MRI 1

Neuroimaging

• Consider MRI of brain and/or spine depending on symptoms to rule out CNS involvement or alternate diagnosis 2

Immediate Medication Review

Discontinue medications that worsen myasthenia gravis 2, 1, 3:

• β-blockers 2, 3
• IV magnesium 2, 3
• Fluoroquinolones 2, 3
• Aminoglycosides 2, 3
• Macrolide antibiotics 2, 3

Neurology Consultation

Obtain neurology consultation for all grades of suspected myasthenia gravis given the potential for progressive disease leading to respiratory compromise 2

Common Pitfalls to Avoid

• Do not delay respiratory assessment: Respiratory failure can develop rapidly and requires immediate recognition using the 20/30/40 rule 1
• Do not assume negative AChR antibodies exclude MG: 15-20% of generalized MG patients are AChR-negative, requiring MuSK and LRP4 testing 1, 4
• Do not overlook cardiac involvement: Concurrent myocarditis can occur, particularly with elevated CPK or troponin 2, 1
• Pupillary involvement should redirect diagnosis: Normal pupils are characteristic of MG; abnormal pupils suggest an alternative diagnosis 1