What is the recommended treatment for a patient with Myasthenia Gravis (MG)?

Myasthenia Gravis Treatment

Begin with pyridostigmine 30 mg orally three times daily as first-line symptomatic treatment, titrating up to a maximum of 120 mg four times daily based on response, and add corticosteroids (prednisone 1-1.5 mg/kg daily) for Grade 2 or higher symptoms that don't respond adequately to pyridostigmine alone. 1, 2, 3

Initial Symptomatic Management

• Start pyridostigmine immediately at 30 mg orally three times daily and gradually increase based on clinical response and tolerability to a maximum of 120 mg orally four times daily. 1, 2, 3
• Pyridostigmine is FDA-approved for myasthenia gravis and works by inhibiting acetylcholinesterase at the neuromuscular junction. 3
• This may be sufficient as monotherapy in mild disease (Grade 1-2 with ocular symptoms only). 1

Escalation to Immunosuppressive Therapy

• Add corticosteroids directly if pyridostigmine provides insufficient control for Grade 2 symptoms (some interference with activities of daily living). 1, 2
• Initiate prednisone at 1-1.5 mg/kg orally daily, with approximately 66-85% of patients showing positive response. 1, 2
• Taper corticosteroids gradually based on symptom improvement. 1
• Consider holding immune checkpoint inhibitors if MG is drug-induced, and may resume only in Grade 2 patients (MGFA class 1-2) if symptoms resolve. 4

Management of Severe Disease (Grade 3-4)

For myasthenic crisis with respiratory compromise, severe generalized weakness, dysphagia, or rapidly progressive symptoms, immediately hospitalize with ICU-level monitoring and initiate acute immunotherapy. 4, 1, 2

• Permanently discontinue any causative immune checkpoint inhibitors. 4
• Administer IVIG 2 g/kg IV over 5 days (0.4 g/kg/day) OR plasmapheresis for 5 days as first-line acute treatment. 4, 1, 2
• Both IVIG and plasmapheresis have comparable efficacy; IVIG may be preferred in pregnant women due to easier administration and fewer monitoring requirements. 1, 2
• Continue corticosteroids (methylprednisolone 1-2 mg/kg daily) concurrently during IVIG or plasmapheresis. 4, 1, 2
• Continue pyridostigmine, but may hold if intubation is required. 1, 2
• Perform frequent pulmonary function assessments with negative inspiratory force and vital capacity monitoring. 4, 1
• Conduct daily neurologic evaluations. 1

Critical Medications to Avoid

Educate patients to strictly avoid medications that worsen myasthenic symptoms through interference with neuromuscular transmission: 4, 1, 2

• β-blockers 4, 1, 2
• Intravenous magnesium 4, 1, 2
• Fluoroquinolone antibiotics 4, 1, 2
• Aminoglycoside antibiotics 4, 1, 2
• Macrolide antibiotics 4, 1, 2
• Metoclopramide 1
• Barbiturate-containing medications (e.g., butalbital) 1

Diagnostic Confirmation Requirements

• Measure acetylcholine receptor (AChR) antibodies and antistriated muscle antibodies in blood as first-line serologic testing. 4, 5, 2
• If AChR antibodies are negative, test for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies. 4, 5, 2
• Perform electrodiagnostic studies including repetitive nerve stimulation and/or single-fiber EMG with jitter studies. 4, 5
• Obtain pulmonary function testing with negative inspiratory force and vital capacity. 4, 1
• Check CPK, aldolase, ESR, CRP to evaluate for possible concurrent myositis. 4
• If respiratory insufficiency or elevated CPK/troponin, perform cardiac examination with ECG and echocardiography for possible concomitant myocarditis. 4

Important Clinical Pitfalls

• Do NOT use IVIG for chronic maintenance therapy - it should be reserved only for acute exacerbations or crisis situations. 1
• Pupils are characteristically NOT affected in myasthenia gravis - pupillary involvement should prompt immediate evaluation for third nerve palsy or other etiologies. 5
• Approximately 50-80% of patients with initial ocular symptoms will develop generalized myasthenia within a few years, requiring vigilant monitoring. 5, 2
• Sequential therapy (plasmapheresis followed by IVIG) is no more effective than either treatment alone and should be avoided. 1
• For patients with thymomas, approximately 30-50% have myasthenia gravis, and mortality in 20% of thymoma patients is related to MG complications. 5

Monitoring and Follow-Up

• Plan regular neurology consultation to adjust treatment as needed. 1
• Teach patients to monitor for and report worsening symptoms including changes in speech/swallowing (bulbar symptoms), respiratory difficulties, and diplopia. 1
• Instruct patients to seek immediate medical attention for significant increase in muscle weakness. 1
• Regular pulmonary function assessment is crucial, especially for patients with generalized disease. 1, 5