What is the treatment for myasthenia gravis?

Treatment of Myasthenia Gravis

The first-line treatment for myasthenia gravis is pyridostigmine, an acetylcholinesterase inhibitor, followed by immunosuppressive therapy with corticosteroids for patients with more than mild symptoms. 1, 2

Diagnostic Workup

Before initiating treatment, a comprehensive diagnostic evaluation should include:

• Antibody testing:

  • AChR antibodies (positive in 80-85% of patients)
  • If AChR negative, test for MuSK and LRP4 antibodies 2, 3
  • Note: Absence of antibodies does not rule out the disease

• Functional assessment:

  • Pulmonary function tests (NIF and VC)
  • CPK, aldolase, ESR, CRP to evaluate for concurrent myositis
  • Electrodiagnostic studies including repetitive stimulation and jitter studies 2

• Additional testing as indicated:

  • Brain/spine MRI to rule out CNS involvement
  • Cardiac evaluation (ECG, troponin, TTE) to assess for myocarditis
  • Inflammatory markers 2

Treatment Algorithm Based on Disease Severity

Grade 2 (Mild Generalized or Ocular Symptoms)

1. Pyridostigmine:

   • Starting dose: 30 mg PO three times daily
   • Titrate up to maximum of 120 mg PO four times daily as tolerated 2
   • Adjust based on symptom response

2. Corticosteroids:

   • Add prednisone 0.5-1.5 mg/kg orally daily if symptoms persist 2
   • Taper based on symptom improvement

3. Monitoring:

   • Neurologic consultation
   • Consider inpatient care as patients can deteriorate quickly 2

Grade 3-4 (Moderate to Severe Generalized Weakness or Myasthenic Crisis)

1. Hospital admission:

   • ICU-level monitoring required
   • Daily neurologic assessment
   • Frequent pulmonary function testing 2

2. Acute interventions:

   • IVIG 2 g/kg IV over 5 days (0.4 g/kg/day) OR
   • Plasmapheresis for 3-5 days 2

3. Corticosteroids:

   • Continue or initiate at higher doses
   • Begin tapering 3-4 weeks after initiation 2

4. Refractory cases:

   • Consider adding rituximab if not responding to IVIG or plasmapheresis 2

Long-term Management

• Immunosuppressive agents:

  • Azathioprine as a steroid-sparing agent 4, 5
  • Other options include mycophenolate, cyclosporine, tacrolimus

• Thymectomy:

  • Beneficial in AChR antibody-positive generalized MG patients up to age 65
  • Always indicated if thymoma is present 3, 5

Important Precautions

• Avoid medications that can worsen myasthenia:

  • Beta-blockers
  • IV magnesium
  • Fluoroquinolones
  • Aminoglycosides
  • Macrolide antibiotics 2

• Monitor for cholinergic side effects of pyridostigmine:

  • Excess tearing, salivation, sweating
  • Abdominal cramping
  • Bradycardia, bronchospasm, hypotension
  • Cardiac arrhythmias (may require muscarinic antagonist like hyoscyamine) 2, 6

• Myasthenic crisis management:

  • Requires immediate hospitalization
  • May need mechanical ventilation
  • Discontinue pyridostigmine temporarily during crisis 7
  • Resume prior to extubation

Special Considerations

• Ocular myasthenia:

  • May respond to pyridostigmine alone
  • Early corticosteroid treatment recommended when ocular motility remains abnormal 5

• Pregnancy:

  • Consider potential teratogenicity of immunosuppressive therapies 5
  • Pyridostigmine generally considered safe

• Elderly patients:

  • Treatment needs to be adjusted based on comorbidities 5
  • Monitor cardiac effects more closely

By following this treatment algorithm, most patients with myasthenia gravis can achieve good symptom control and many can reach remission or minimal manifestation status.