What are the diagnosis and treatment options for Myasthenia Gravis?

Myasthenia Gravis: Diagnosis and Treatment

Diagnostic Approach

The diagnosis of myasthenia gravis requires serologic testing for acetylcholine receptor (AChR) antibodies and antistriated muscle antibodies as the initial step, followed by electrodiagnostic confirmation with repetitive nerve stimulation or single-fiber EMG. 1

Essential Serologic Testing

• Obtain AChR antibodies and antistriated muscle antibodies in blood first - these are positive in 80-85% of patients 1, 2
• If AChR antibodies are negative, test for muscle-specific kinase (MuSK) antibodies (positive in 5-8% of patients) and lipoprotein-related protein 4 (LRP4) antibodies (positive in <1%) 1, 2
• Approximately 10% of patients remain seronegative for all known antibodies 2

Electrodiagnostic Studies

• Single-fiber EMG is the gold standard with >90% sensitivity in ocular myasthenia 3
• Repetitive nerve stimulation testing is positive in only one-third of patients with ocular myasthenia 3
• Include neuromuscular junction testing with repetitive stimulation and/or jitter studies, nerve conduction studies to exclude neuropathy, and needle EMG to evaluate for concurrent myositis 1

Additional Diagnostic Workup

• Pulmonary function assessment with negative inspiratory force and vital capacity - critical given the risk of respiratory compromise 1, 4
• Creatine phosphokinase (CPK), aldolase, ESR, and CRP to evaluate for possible concurrent myositis 1
• If respiratory insufficiency or elevated CPK/troponin T present, perform ECG and transthoracic echocardiogram to rule out concomitant myocarditis 1
• Consider MRI of brain and/or spine depending on symptoms to rule out CNS involvement or alternative diagnosis 1
• Mandatory neurology consultation 1

Clinical Pearls for Diagnosis

• The ice test (applying ice pack over closed eyes for 2 minutes) is highly specific for myasthenia gravis, particularly for ocular symptoms 5
• Look for fatigable or fluctuating muscle weakness, generally more proximal than distal 5
• Ocular involvement (ptosis, extraocular movement abnormalities) and bulbar symptoms (dysphagia, dysarthria, facial weakness) are common presentations 5, 6

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Treatment Algorithm

Grade 2 Disease (Moderate Symptoms)

Start pyridostigmine at 30 mg orally three times daily and titrate gradually to a maximum of 120 mg orally four times daily based on symptom response and tolerability. 1, 7

• Pyridostigmine is FDA-approved for myasthenia gravis treatment 7
• Hold immune checkpoint inhibitors if applicable and may resume only if symptoms resolve 1
• Approximately 50% of patients with ocular myasthenia show minimal response to pyridostigmine alone and will require escalation 3, 5

If pyridostigmine provides insufficient control in Grade 2 symptoms, add corticosteroids directly with prednisone 1 to 1.5 mg/kg orally daily. 1

• Corticosteroids are effective in approximately 66-85% of patients 3
• Wean corticosteroids gradually based on symptom improvement 1, 3

Grade 3-4 Disease (Severe/Crisis)

Immediately hospitalize patients with myasthenic crisis, potentially requiring ICU monitoring, and initiate IVIG 2 g/kg total dose over 5 days (0.4 g/kg/day × 5 days) OR plasmapheresis for 5 days. 1, 4

• Permanently discontinue immune checkpoint inhibitors if applicable 1
• Continue corticosteroids concurrently during IVIG or plasmapheresis 1, 4
• Maintain pyridostigmine unless contraindicated 4
• Perform frequent pulmonary function assessments with negative inspiratory force and vital capacity monitoring 1, 4
• Conduct daily neurologic evaluations 1, 4

Long-Term Immunosuppressive Therapy

Azathioprine is an effective immunosuppressant for long-term maintenance therapy in patients requiring steroid-sparing agents 3, 8

• Other options include mycophenolate mofetil and tacrolimus 8
• Efgartigimod alfa-fcab has been recently FDA-approved for AChR-antibody positive patients 3, 8
• Rituximab is particularly effective for MuSK-antibody positive patients 8, 2

Thymectomy Considerations

• Thymectomy improves clinical outcomes in selected patients with nonthymomatous MG who are AChR-antibody positive, up to age 65 years 8, 9
• 10-20% of AChR-positive patients have thymoma, usually detected at disease onset 2
• All patients with suspected thymoma must have serum AChR antibody levels measured preoperatively to avoid respiratory failure during anesthesia 5

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Critical Medications to Avoid

Strictly avoid medications that worsen myasthenic symptoms: β-blockers, intravenous magnesium, fluoroquinolone antibiotics, aminoglycoside antibiotics, and macrolide antibiotics. 1, 4

• These medications can precipitate myasthenic crisis 1
• Educate patients to inform all healthcare providers about their diagnosis before receiving any new medications 4
• Exercise caution with anesthetic agents in patients with respiratory muscle weakness 3

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Important Clinical Pitfalls

IVIG Misuse

• IVIG should NOT be used for chronic maintenance therapy in myasthenia gravis 4
• IVIG is reserved exclusively for acute exacerbations (Grade 3-4) or crisis situations requiring hospitalization 4
• The correct dose is 2 g/kg total over 5 days, not ongoing maintenance dosing 4

Monitoring Requirements

• Regular pulmonary function assessment is crucial, especially in patients with generalized disease, as 50-80% of patients with initial ocular symptoms may develop generalized myasthenia within a few years 5, 4
• In approximately 20% of thymoma patients, mortality is related to myasthenia gravis complications 5

Treatment Response Timeline

• Approximately 50% of patients with ocular myasthenia may require escalation to corticosteroids due to minimal pyridostigmine response 3, 5
• Azathioprine and other oral immunosuppressants have delayed onset of action and require patience 9

Special Populations

• Collaboration between experienced ophthalmologist and neurologist is necessary for diagnosis and management, particularly in patients with ocular involvement 3, 5
• Consider teratogenicity of certain therapies in women of childbearing age 9
• Adjust treatment approach in elderly patients based on comorbidities 9