What is the initial treatment for Myasthenia Gravis (MG)?

Initial Treatment for Myasthenia Gravis

Pyridostigmine bromide is the recommended first-line treatment for myasthenia gravis, starting at 30 mg PO three times daily and gradually increasing to a maximum of 120 mg PO four times daily as tolerated based on symptoms. 1, 2

Diagnostic Approach Before Treatment

Before initiating treatment, confirm the diagnosis with:

• Acetylcholine receptor (AChR) antibody testing (sensitivity 80-85% in generalized MG, 40-77% in ocular MG) 1
• If AChR antibodies are negative, test for muscle-specific kinase (MuSK) antibodies (positive in 5-8% of cases) 1
• Electrodiagnostic studies including neuromuscular junction testing with repetitive stimulation and/or jitter studies 3, 1
• Pulmonary function assessment with negative inspiratory force and vital capacity 3
• Laboratory tests: CPK, aldolase, ESR, CRP to evaluate for concurrent myositis 3, 1
• Chest imaging to evaluate for thymoma (present in 10-20% of AChR-positive patients) 1

Treatment Algorithm

Step 1: Symptomatic Treatment

• Pyridostigmine bromide (acetylcholinesterase inhibitor)
  • Starting dose: 30 mg PO three times daily
  • Gradually increase to maximum of 120 mg PO four times daily as tolerated 3, 1, 2
  • May be sufficient for mild disease 4
  • Sustained-release formulation can reduce dosing frequency and improve quality of life 5

Step 2: For Moderate to Severe Disease or Inadequate Response to Pyridostigmine

• Add corticosteroids (prednisone 0.5-1.5 mg/kg orally daily) 1, 4
  • 66-85% of patients show positive response 1
  • Consider initiating steroid-sparing agents concurrently to minimize steroid exposure:
    • Azathioprine (2 mg/kg of ideal body weight in divided doses)
    • Mycophenolate mofetil (500 mg twice daily increasing to 1000 mg twice daily)
    • Methotrexate (15 mg weekly) 1

Step 3: For Myasthenic Crisis or Severe Symptoms

• Intravenous immunoglobulin (IVIG) (2 g/kg over 5 days) OR
• Plasmapheresis for 5 days 3, 1
• Consider ICU monitoring for respiratory compromise 3

Step 4: For Refractory Cases

• Rituximab for patients not responding to conventional immunosuppression 1, 6
• Thymectomy for patients with thymoma or AChR antibody-positive generalized MG up to age 65 1, 4

Special Considerations

Medication Precautions

• Avoid medications that can worsen myasthenia gravis:
  • β-blockers
  • IV magnesium
  • Fluoroquinolones
  • Aminoglycosides
  • Macrolides 3, 1

Monitoring

• Regular neurological assessments when starting or adjusting medications
• Monitor for signs of:
  • Cholinergic crisis (increased weakness due to overdosage of pyridostigmine)
  • Myasthenic crisis (increased weakness due to worsening disease) 2
• Regular pulmonary function testing in patients with moderate to severe disease 1

Treatment Based on MG Subtype

• Ocular MG: Pyridostigmine first-line; add corticosteroids if persistent diplopia 4
• Generalized MG: More aggressive immunosuppression often required 4, 7
• MuSK antibody-positive MG: May have poorer response to acetylcholinesterase inhibitors and may require earlier immunosuppression 1

Important Pitfalls to Avoid

1. Failure to distinguish between cholinergic crisis and myasthenic crisis:

   • Cholinergic crisis (overdosage) requires reducing or stopping pyridostigmine
   • Myasthenic crisis (disease worsening) requires intensifying treatment 2

2. Inadequate monitoring of respiratory function:

   • Progressive MG can lead to respiratory compromise; regular pulmonary function assessment is essential 3

3. Delayed initiation of immunosuppression:

   • While pyridostigmine provides symptomatic relief, it does not modify disease course; early immunosuppression may be necessary in moderate to severe disease 4, 8

4. Overlooking thymectomy as a treatment option:

   • Thymectomy should be considered in AChR antibody-positive generalized MG patients up to age 65 1, 4