What is the diagnostic workup and treatment for a patient suspected of having myasthenia gravis?

Myasthenia Gravis Diagnosis and Treatment

Diagnostic Workup

The diagnostic workup for suspected myasthenia gravis should 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, 2

Initial Clinical Assessment

• Look for fatigable or fluctuating muscle weakness, typically more proximal than distal, with characteristic ocular involvement (ptosis, diplopia), bulbar symptoms (dysphagia, dysarthria, facial weakness), or generalized limb weakness 2, 3
• Confirm pupils are NOT affected - pupillary involvement immediately suggests an alternative diagnosis such as third nerve palsy rather than myasthenia gravis 2
• Perform the ice pack test for patients with ptosis: apply ice over closed eyes for 2 minutes, which is highly specific for myasthenia gravis if ptosis improves 2

Laboratory Testing

• First-line: AChR antibodies (positive in 80-85% of generalized MG, but only 40-77% of ocular MG) 2, 3
• If AChR negative: test for muscle-specific kinase (MuSK) antibodies (5-8% of patients) and lipoprotein-related protein 4 (LRP4) antibodies (<1%) 1, 2, 3
• Check CPK, aldolase, ESR, and CRP to evaluate for concurrent myositis 1
• If respiratory insufficiency or elevated CPK/troponin: perform cardiac workup with ECG and echocardiogram to rule out myocarditis 1

Electrodiagnostic Studies

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

Pulmonary Function Assessment

• Measure negative inspiratory force (NIF) and vital capacity (VC) at baseline in all patients 1, 4
• 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 4

Additional Testing

• Neurology consultation is mandatory for all suspected cases 1
• Consider MRI of brain/spine if symptoms suggest CNS involvement or to exclude alternative diagnoses 1
• Chest CT to evaluate for thymoma (present in 10-20% of AChR-positive patients) 2, 3

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Treatment Algorithm

Grade 2 (Moderate Symptoms)

Start with pyridostigmine 30 mg orally three times daily, titrating up to a maximum of 120 mg four times daily based on symptom response. 1, 2, 5, 6

• Hold checkpoint inhibitors if applicable and may resume only if symptoms resolve to Grade 1 1
• Escalate directly to corticosteroids (prednisone 1-1.5 mg/kg daily) if pyridostigmine provides insufficient control 1, 5
• Taper steroids gradually over 3-4 weeks based on symptom improvement 1, 4
• Consider thymectomy in non-thymoma patients up to age 50-65 years if not achieving remission on symptomatic treatment 7

Grade 3-4 (Severe/Crisis)

Immediately hospitalize with ICU-level monitoring, permanently discontinue checkpoint inhibitors if applicable, and initiate IVIG (2 g/kg over 5 days) or plasmapheresis (5 sessions over 5 days) along with high-dose corticosteroids. 1, 4, 5

• Administer methylprednisolone 1-2 mg/kg/day IV or prednisone 1-1.5 mg/kg/day orally 4
• IVIG dosing: 0.4 g/kg/day for 5 consecutive days (total 2 g/kg) 4, 5
• Continue pyridostigmine in non-intubated patients; discontinue in intubated patients 4
• Perform daily neurologic evaluations 1, 4
• Monitor respiratory function frequently with NIF and VC measurements 1, 4

Long-Term Immunosuppression

Combine low-dose corticosteroids with azathioprine as first-line maintenance therapy, with rituximab as an alternative first-line option, particularly for MuSK-positive patients. 8, 7

• Second-line options include mycophenolate mofetil, methotrexate, and tacrolimus 8, 7
• Do NOT use IVIG for chronic maintenance therapy - it is reserved only for acute exacerbations or crisis situations 5

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Critical Medications to AVOID

Immediately discontinue and educate patients to avoid: β-blockers, IV magnesium (absolutely contraindicated), fluoroquinolones, aminoglycosides, and macrolide antibiotics. 1, 2, 4, 5

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Special Considerations

• 50-80% of patients with isolated ocular symptoms will develop generalized myasthenia within a few years, requiring close monitoring 2
• Checkpoint inhibitor-associated myasthenia may be monophasic, potentially requiring less prolonged immunosuppression 1, 4
• Thymectomy improves clinical outcomes in selected non-thymomatous patients, particularly those under 50-65 years 8, 7
• Sequential therapy (plasmapheresis followed by IVIG) is no more effective than either alone and should be avoided 5