What are the initial and subsequent treatment options for managing myasthenia gravis?

Management of Myasthenia Gravis

Start all patients with symptomatic myasthenia gravis on pyridostigmine 30 mg orally three times daily, titrating up to a maximum of 120 mg four times daily based on response, and escalate to corticosteroids (prednisone 1-1.5 mg/kg daily) for Grade 2 or higher symptoms that persist despite pyridostigmine optimization. 1, 2, 3

Initial Symptomatic Treatment

• Begin pyridostigmine (Mestinon) at 30 mg orally three times daily as first-line therapy for all patients with confirmed myasthenia gravis, regardless of whether disease is ocular or generalized 1, 3
• Gradually increase the dose based on clinical response and tolerability, with a maximum dosing of 120 mg orally four times daily 1, 2
• Approximately 50% of patients with ocular myasthenia may show minimal response to pyridostigmine alone and will require escalation to corticosteroids 1
• For IV administration in hospitalized patients, 30 mg oral pyridostigmine corresponds to 1 mg IV or 0.75 mg neostigmine IM 4

Escalation to Immunosuppressive Therapy

For Grade 2 symptoms (moderate weakness affecting activities of daily living), add corticosteroids directly if pyridostigmine provides insufficient control:

• Start prednisone at 1-1.5 mg/kg orally daily 1, 2
• Approximately 66-85% of patients show a positive response to corticosteroids 1
• Begin steroid taper 3-4 weeks after initiation, based on symptom improvement 4
• Consider azathioprine as a third-line steroid-sparing agent for patients with moderate to severe disease 1

Management of Myasthenic Crisis (Grade 3-4)

For severe exacerbations with respiratory compromise or severe generalized weakness, immediately hospitalize with ICU-level monitoring and initiate rapid immunotherapy:

• Admit to ICU for close respiratory monitoring with frequent pulmonary function assessments (negative inspiratory force and vital capacity) 4, 2
• Apply the "20/30/40 rule" to identify patients at risk of respiratory failure: vital capacity <20 ml/kg, maximum inspiratory pressure <30 cmH₂O, or maximum expiratory pressure <40 cmH₂O 4
• Administer high-dose corticosteroids: methylprednisolone 1-2 mg/kg/day IV or prednisone 1-1.5 mg/kg/day orally 4
• Initiate either IVIG (2 g/kg total dose over 5 days at 0.4 g/kg/day) OR plasmapheresis (5 sessions over 5 days) - both are equally effective 4, 2
• Sequential therapy (plasmapheresis followed by IVIG) is no more effective than either treatment alone and should be avoided 2
• Discontinue or withhold pyridostigmine in intubated patients 4
• For non-intubated patients with myasthenic symptoms during crisis, pyridostigmine may be continued starting from 30 mg orally up to 600 mg daily 4

Critical Medications to Avoid

Immediately discontinue these medications that can precipitate myasthenic crisis:

• Beta-blockers (absolutely contraindicated) 4, 1
• IV magnesium (absolutely contraindicated - if severe hypomagnesemia requires treatment, neurology consultation is mandatory before administration) 4
• Fluoroquinolone antibiotics 4, 1, 2
• Aminoglycoside antibiotics 4, 1, 2
• Macrolide antibiotics 4, 1, 2
• Barbiturate-containing medications like Fioricet (butalbital and acetaminophen) 2

Diagnostic Workup Requirements

Confirm diagnosis before initiating immunosuppressive therapy:

• Check acetylcholine receptor (AChR) antibodies and anti-striated muscle antibodies (present in 80-85% of patients) 4, 1
• If AChR antibodies are negative, test for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies 4, 1
• Perform electrodiagnostic studies with repetitive nerve stimulation and/or single-fiber EMG (>90% sensitivity for ocular myasthenia) 1
• The ice test (applying ice pack over closed eyes for 2 minutes) is highly specific for myasthenia gravis, particularly for ocular symptoms 1
• Obtain chest imaging to evaluate for thymoma (present in 10-20% of AChR-positive patients) 1

Monitoring and Follow-up

• Perform pulmonary function assessment every 6 months in patients with stable disease 4
• For patients with moderate to severe generalized weakness (MGFA class III-V), conduct frequent pulmonary function assessments with NIF and VC 4
• The single breath count test can be used to assess respiratory muscle function, with counting to ≥25 correlating with normal respiratory muscle function 4
• Daily neurological evaluation during acute exacerbations 4
• Regular neurology consultation to adjust treatment as needed 2

Special Considerations for Thymectomy

• Thymectomy is beneficial in patients with AChR antibody-positive generalized myasthenia gravis, up to age 65 years 5
• All patients with thymoma should undergo thymectomy, as approximately 30-50% of thymoma patients have myasthenia gravis 1
• Measure serum anti-acetylcholine receptor antibody levels preoperatively in any patient with suspected myasthenia gravis requiring surgery to avoid respiratory failure during anesthesia 1

Important Clinical Pitfalls

• Pupils are characteristically NOT affected in myasthenia gravis - presence of pupillary involvement should immediately prompt evaluation for third nerve palsy or other etiologies 1
• Approximately 50-80% of patients presenting with isolated ocular symptoms will develop generalized myasthenia within a few years, making accurate diagnosis essential for preventing life-threatening respiratory failure 1
• IVIG should NOT be used for chronic maintenance therapy in myasthenia gravis - it is reserved for acute exacerbations or crisis situations 2
• Monitor patients for a minimum of 24 hours in ICU, HDU, or recovery unit even after apparent stabilization from myasthenic crisis 4