What is the initial treatment for myasthenia gravis?

Initial Treatment for Myasthenia Gravis

Start pyridostigmine (Mestinon) at 30 mg orally three times daily as first-line symptomatic treatment, titrating gradually to a maximum of 120 mg four times daily based on clinical response. 1, 2

Symptomatic Treatment Algorithm

Pyridostigmine is the cornerstone of initial management for all patients with myasthenia gravis, as it enhances neuromuscular transmission by inhibiting acetylcholinesterase. 2, 3

• Begin at 30 mg orally three times daily 1
• Titrate upward based on symptom control and tolerability 1
• Maximum dosing: 120 mg orally four times daily 1
• Instruct patients to time activities around medication dosing for optimal strength 1

Important caveat: Pyridostigmine alone may be sufficient only in mild disease (MGFA Class 1 ocular symptoms). 1, 3 Approximately 50% of patients with ocular myasthenia show minimal response to pyridostigmine alone and require escalation to immunosuppressive therapy. 4

When to Escalate to Immunosuppressive Therapy

Add corticosteroids for Grade 2 symptoms (mild generalized weakness interfering with activities of daily living) if pyridostigmine provides insufficient control. 1

• Prednisone 1-1.5 mg/kg orally daily 5, 1
• Taper gradually based on symptom improvement 1
• Critical warning: Corticosteroids can paradoxically worsen symptoms when initiated, particularly at high doses, requiring close monitoring. 6

Management of Severe Disease (Grade 3-4)

For myasthenic crisis with respiratory compromise, dysphagia, or rapidly progressive symptoms, immediately hospitalize with ICU-level monitoring. 5, 1

• Permanently discontinue any triggering medications 5
• Initiate IVIG 2 g/kg IV over 5 days (0.4 g/kg/day) OR plasmapheresis for 5 days 5, 1
• Continue corticosteroids (methylprednisolone 1-2 mg/kg daily) 5
• Maintain pyridostigmine 5
• Perform frequent pulmonary function assessment (vital capacity, negative inspiratory force) 5, 1
• Daily neurologic evaluations 5

Critical Medications to Avoid

Educate all patients to strictly avoid medications that precipitate myasthenic crisis: 5, 1, 6

• β-blockers (all formulations, especially IV) 5, 6
• IV magnesium 5, 6
• Fluoroquinolone antibiotics 5, 6
• Aminoglycoside antibiotics (tobramycin, gentamicin, amikacin) 5, 6
• Macrolide antibiotics (erythromycin, azithromycin, clarithromycin) 5, 6
• Barbiturate-containing medications like Fioricet (butalbital/acetaminophen) 1, 6

These medications can precipitate life-threatening myasthenic crisis requiring mechanical ventilation. 6

Diagnostic Confirmation Requirements

Before initiating treatment, confirm diagnosis with: 1, 4

• Acetylcholine receptor (AChR) antibodies and antistriated muscle antibodies 1
• If AChR antibodies negative, test for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies 1
• Electrodiagnostic studies with repetitive stimulation and/or single-fiber EMG (>90% sensitivity for ocular myasthenia) 5, 4
• Pulmonary function testing with negative inspiratory force and vital capacity 1

Monitoring and Follow-up

• Regular neurologic consultation to adjust treatment 1
• Monitor for worsening symptoms: changes in speech/swallowing (bulbar symptoms), respiratory difficulties, diplopia 1
• Critical warning: 50-80% of patients with initial ocular symptoms develop generalized myasthenia within a few years, requiring ongoing respiratory function monitoring. 4
• Teach patients to seek immediate medical attention for significant increase in muscle weakness 1

Common Pitfalls

Do not use IVIG for chronic maintenance therapy in myasthenia gravis—it should be reserved only for acute exacerbations or crisis situations. 1 Sequential therapy (plasmapheresis followed by IVIG) is no more effective than either treatment alone and should be avoided. 1

Pyridostigmine can cause cardiac side effects including bradycardia, AV block, and rarely myocardial infarction (particularly in elderly females), requiring cardiac monitoring if symptoms develop. 7, 8