What is the initial treatment for myasthenia gravis?

Initial Treatment for Myasthenia Gravis

Start pyridostigmine 30 mg orally three times daily as first-line symptomatic treatment, titrating upward based on clinical response to a maximum of 120 mg four times daily. 1, 2, 3

Stepwise Treatment Algorithm

First-Line: Symptomatic Treatment with Acetylcholinesterase Inhibitors

• Pyridostigmine (Mestinon) is FDA-approved and recommended as initial therapy for all patients with myasthenia gravis. 1, 3
• Begin at 30 mg orally three times daily and gradually increase based on symptom response and tolerability. 1, 2
• Maximum dosing is 120 mg orally four times daily (total 480 mg/day). 1
• Instruct patients to time activities around medication dosing for optimal strength. 1
• This may be sufficient as monotherapy in mild disease. 4

Critical caveat: Pyridostigmine provides only symptomatic relief and does not modify the underlying autoimmune disease process. 5 Most patients with more than mild disease will eventually require immunosuppressive therapy. 4, 5

Second-Line: Add Corticosteroids for Inadequate Response

• If pyridostigmine provides insufficient symptom control (Grade 2 symptoms), add prednisone 1-1.5 mg/kg orally daily. 1, 2
• Approximately 66-85% of patients show positive response to corticosteroids. 2
• Taper gradually based on symptom improvement, typically beginning 3-4 weeks after initiation. 1, 6
• Continue pyridostigmine concurrently during corticosteroid therapy. 1

Third-Line: Long-Term Immunosuppression

• For patients requiring chronic immunosuppression or those with steroid-refractory disease, add azathioprine as a steroid-sparing agent. 2, 7
• Other options include cyclosporine, mycophenolate mofetil, methotrexate, or tacrolimus. 7

Management of Severe Exacerbations (Grade 3-4 Crisis)

For myasthenic crisis with respiratory compromise or severe generalized weakness, immediately hospitalize with ICU-level monitoring and initiate IVIG or plasmapheresis. 1, 6

Crisis Protocol:

• Admit to ICU for close respiratory monitoring. 1, 6
• Perform immediate pulmonary function assessment with negative inspiratory force (NIF) and vital capacity (VC). 6
• 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. 6
• Administer IVIG 2 g/kg total dose over 5 days (0.4 g/kg/day × 5 days) OR plasmapheresis (5 sessions over 5 days). 1, 6
• Start high-dose corticosteroids: methylprednisolone 1-2 mg/kg/day IV or prednisone 1-1.5 mg/kg/day orally. 6
• Pyridostigmine may be continued during crisis but should be discontinued or withheld if intubation is required. 1, 6
• Perform daily neurologic evaluations and frequent pulmonary function assessments. 1

Important note: Sequential therapy (plasmapheresis followed by IVIG) is no more effective than either treatment alone and should be avoided. 1 IVIG should NOT be used for chronic maintenance therapy. 1

Critical Medications to Avoid

Immediately discontinue and strictly avoid medications that worsen myasthenic symptoms: 1, 2, 6

• β-blockers 1, 6
• IV magnesium (absolutely contraindicated) 6
• Fluoroquinolone antibiotics 1, 2, 6
• Aminoglycoside antibiotics 1, 2, 6
• Macrolide antibiotics 1, 2, 6
• Barbiturate-containing medications (e.g., butalbital) 1

Essential Diagnostic Workup

• Confirm diagnosis with acetylcholine receptor (AChR) antibodies and anti-striated muscle antibodies. 1, 2, 6
• If AChR antibodies are negative, test for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies. 1, 6
• Perform baseline pulmonary function testing with NIF and VC. 1, 6
• Consider electrodiagnostic studies with repetitive stimulation and/or single-fiber EMG (>90% sensitivity for ocular myasthenia). 2

Monitoring Requirements

• Regular neurology follow-up to adjust treatment as needed. 1
• Monitor for worsening bulbar symptoms (speech, swallowing), respiratory difficulties, and diplopia. 1
• Pulmonary function assessment every 6 months in stable disease, more frequently in moderate-severe disease. 6
• Approximately 50-80% of patients with initial ocular symptoms will develop generalized myasthenia within a few years, requiring vigilant monitoring. 2

Special Considerations

Pyridostigmine cardiac risk: Rare cases of myocardial infarction have been reported, particularly in elderly females, due to coronary vasospasm or arrhythmogenic effects from excess acetylcholine. 8 Monitor for chest pain, especially when initiating therapy in older patients with cardiovascular risk factors.

Conversion for IV administration: If oral intake is not possible, 30 mg oral pyridostigmine corresponds to 1 mg IV pyridostigmine or 0.75 mg neostigmine IM. 1, 6