What is the recommended management for Myasthenia Gravis?

Management of Myasthenia Gravis

The recommended first-line treatment for myasthenia gravis is pyridostigmine starting at 30 mg orally three times daily, gradually increasing to a maximum of 120 mg orally four times daily as tolerated and based on symptoms, with additional immunosuppressive therapy for patients with more than mild disease. 1

Diagnostic Workup

• Neurology consultation is essential
• Diagnostic tests include:
  • Ice pack test
  • Edrophonium (Tensilon) test
  • Repetitive nerve stimulation
  • Single-fiber electromyography (SFEMG) - considered the gold standard with >90% sensitivity 1
  • Antibody testing (acetylcholine receptor antibodies)
  • Chest imaging to evaluate for thymoma

Treatment Algorithm

Step 1: Symptomatic Treatment

• Pyridostigmine (Mestinon)
  • Starting dose: 30 mg PO three times daily
  • Gradually increase to maximum of 120 mg four times daily (up to 600 mg daily in severe cases) 1
  • Monitor for cholinergic side effects (diarrhea, abdominal cramps, hypersalivation, sweating) 2
  • Warning: Overdosage can lead to cholinergic crisis with increasing muscle weakness affecting respiration 3

Step 2: For Patients with More Than Mild Disease

• Add corticosteroids:
  • Prednisone 1-1.5 mg/kg PO daily 4, 1
  • 66-85% of patients show positive response to corticosteroids 1
  • Wean based on symptom improvement

Step 3: Steroid-Sparing Agents

• Initiate concurrently with corticosteroids to minimize steroid exposure:
  • Azathioprine: 2 mg/kg of ideal body weight in divided doses 1, 5
  • Methotrexate: 15 mg weekly 1
  • Mycophenolate mofetil: 500 mg twice daily increasing to 1000 mg twice daily 1

Step 4: For Refractory Cases or Crisis

• For myasthenic crisis:
  • Hospital admission, possibly ICU monitoring
  • IVIG 2 g/kg over 5 days OR
  • Plasmapheresis for 5 days 4
• For refractory disease:
  • Consider rituximab 6
  • Newer targeted therapies like eculizumab or ravulizumab 7

Special Considerations

Thymectomy

• Indicated for patients with thymoma
• Beneficial in AChR antibody-positive generalized MG up to age 65 6
• Minimally invasive approaches including robotic-assisted surgery are available

Monitoring

• Regular neurological assessments
• Pulmonary function assessment with negative inspiratory force (NIF) and vital capacity (VC)
  • NIF > -60 cm H₂O: Continue routine monitoring
  • NIF -20 to -60 cm H₂O: Close monitoring and potential intervention 1

Medication Precautions

• Avoid medications that can worsen myasthenia:
  • β-blockers
  • IV magnesium
  • Fluoroquinolones
  • Aminoglycosides
  • Macrolides 4

Distinguishing Myasthenic vs. Cholinergic Crisis

• Myasthenic crisis: Worsening disease requiring more anticholinesterase therapy
• Cholinergic crisis: Overdose of anticholinesterase medications requiring immediate withdrawal of these drugs and possible atropine administration 3
• Edrophonium test may help differentiate between the two types of crisis

Side Effects of Pyridostigmine

• 91% of patients report side effects 2
• Most common: flatulence, urinary urgency, muscle cramps, blurred vision, hyperhidrosis
• Reasons for discontinuation: diarrhea, abdominal cramps, muscle twitching 2

The management of myasthenia gravis requires careful titration of medications and close monitoring for both disease progression and medication side effects. Early consultation with neurology is essential, and treatment should be escalated based on symptom severity and response to initial therapy.