What is the management of myasthenia gravis?

Management of Myasthenia Gravis

The first-line treatment for myasthenia gravis is pyridostigmine, starting at 30 mg orally three times daily and gradually increasing to a maximum of 120 mg four times daily based on symptom response, with further management escalating to immunosuppressive therapy for inadequate symptom control. 1

Diagnostic Confirmation

• Diagnosis should be confirmed with:
  • Electrodiagnostic studies (repetitive nerve stimulation)
  • Single-fiber EMG (gold standard with >90% sensitivity)
  • Antibody testing (AChR antibodies)
  • Chest imaging to evaluate for thymoma 1

Treatment Algorithm

Step 1: Symptomatic Treatment

• Pyridostigmine (acetylcholinesterase inhibitor)
  • Starting dose: 30 mg orally three times daily
  • Titrate based on symptoms up to 120 mg four times daily
  • Maximum daily dose: 600 mg 1, 2
  • Monitor for cholinergic side effects (diarrhea, abdominal cramps, increased secretions)

Warning: Overdosage of pyridostigmine can result in cholinergic crisis, characterized by increasing muscle weakness that may lead to respiratory failure. Distinguishing between myasthenic crisis (disease worsening) and cholinergic crisis (medication overdose) is critical as management differs radically. 2

Step 2: Immunosuppressive Therapy (for inadequate response to pyridostigmine)

• Corticosteroids:

  • Prednisone 0.5-1.5 mg/kg orally daily
  • 66-85% of patients show positive response 1

• Steroid-sparing agents (should be initiated concurrently with corticosteroids):

  • Methotrexate: 15 mg weekly
  • Azathioprine: 2 mg/kg ideal body weight in divided doses
  • Mycophenolate mofetil: Start 500 mg twice daily, increase to 1000 mg twice daily 1, 3

Step 3: Rapid Intervention for Crisis

• For myasthenic crisis:
  • Plasmapheresis or intravenous immunoglobulin (IVIG) 3, 4
  • In settings where these are unavailable, continuous IV pyridostigmine or neostigmine may be considered with careful monitoring 4

Step 4: Surgical Management

• Thymectomy indicated for:
  • Patients with thymoma
  • AChR antibody-positive generalized MG up to age 65
  • Reported remission rates of approximately 11.6% after thymectomy 1, 3
• Minimally invasive techniques including robotic-assisted approaches are now available 3

Monitoring and Follow-up

• Regular neurological assessments
• Respiratory function monitoring:
  • Negative Inspiratory Force (NIF) measurements
  • Interpretation guidelines:
    • NIF > -60 cm H₂O: Continue routine monitoring
    • NIF -20 to -60 cm H₂O: Close monitoring and potential intervention 1
• Forced Vital Capacity (FVC) assessment
• Regular follow-up with neuromuscular specialist 1

Special Considerations

Anesthesia Management

• Safe anesthetic agents:

  • Propofol, sevoflurane, isoflurane
  • Fentanyl, remifentanil
  • Lidocaine, bupivacaine 1

• Avoid:

  • Atracurium, mivacurium, and succinylcholine 1

• Preferred neuromuscular blocker:

  • Rocuronium (can be antagonized with sugammadex) 1

Myasthenic vs. Cholinergic Crisis

• Myasthenic crisis: Increase in disease severity requiring intensification of therapy
• Cholinergic crisis: Overdose of acetylcholinesterase inhibitors requiring immediate withdrawal of these medications and possible atropine administration
• Differentiation may require edrophonium (Tensilon) test 2

Refractory MG

• Consider rituximab for refractory cases 3, 5
• Newer targeted therapies:
  • Eculizumab and ravulizumab (complement inhibitors) are approved in some countries 5

Management of Ocular MG

• Pyridostigmine for symptomatic control
• Early corticosteroid treatment when ocular motility is abnormal and unresponsive to symptomatic treatment 3

Pregnancy Considerations

• Pyridostigmine use during pregnancy requires weighing potential benefits against possible risks to mother and child 2
• Certain immunosuppressants may be teratogenic and require careful consideration in women of childbearing age 3