What is the initial treatment for Myasthenia Gravis?

Initial Treatment for Myasthenia Gravis

The initial treatment for myasthenia gravis should be pyridostigmine (Mestinon), starting at 30 mg orally three times daily and gradually increasing to a maximum of 120 mg orally four times daily as tolerated and based on symptom response. 1, 2, 3

Diagnostic Workup Before Treatment

• Obtain acetylcholine receptor (AChR) and antistriated muscle antibodies in blood; if AChR antibodies are negative, consider muscle-specific kinase and lipoprotein-related 4 antibodies 4, 1
• Perform pulmonary function assessment with negative inspiratory force and vital capacity to establish baseline respiratory function 4
• Check creatine phosphokinase (CPK), aldolase, ESR, and CRP to evaluate for possible concurrent myositis 4
• Consider MRI of brain and/or spine depending on symptoms to rule out CNS involvement 4
• Obtain neurology consultation for expert evaluation 4, 1
• Conduct electrodiagnostic studies, including neuromuscular junction testing with repetitive stimulation and/or jitter studies 4, 1

Treatment Algorithm Based on Disease Severity

Mild Disease (Ocular Symptoms Only - MGFA Class 1)

1. First-line: Pyridostigmine

   • Start at 30 mg orally three times daily 1, 2
   • Gradually increase to maximum of 120 mg orally four times daily as tolerated 1, 2
   • Approximately 50% of patients with ocular myasthenia may show minimal response to pyridostigmine alone 1

2. If inadequate response after optimal pyridostigmine dosing:

   • Add prednisone 1-1.5 mg/kg orally daily 4, 1
   • Wean based on symptom improvement 4

Moderate Disease (Mild Generalized Weakness - MGFA Class 2)

1. First-line: Pyridostigmine as above 4, 1
2. Second-line: Add corticosteroids
   • Prednisone 1-1.5 mg/kg orally daily 4, 2
   • Approximately 66-85% of patients show positive response to corticosteroids 1

Severe Disease (Moderate to Severe Generalized Weakness - MGFA Class 3-4)

1. Hospitalize patient (may need ICU-level monitoring) 4
2. Administer corticosteroids (prednisone or methylprednisolone 1-2 mg/kg daily) 4
3. Initiate IVIG (2 g/kg IV over 5 days) or plasmapheresis for 5 days 4, 2
4. Perform frequent pulmonary function assessment 4
5. Conduct daily neurological evaluation 4

Important Considerations and Potential Pitfalls

• Avoid medications that can worsen myasthenia symptoms: β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolides 4, 1, 2
• Monitor for side effects of pyridostigmine: Most common include flatulence, urinary urgency, muscle cramps, blurred vision, and hyperhidrosis 5
• Be aware of potential cardiac complications: Pyridostigmine can rarely precipitate myocardial ischemia in elderly patients with underlying coronary artery disease 6
• Consider sustained-release pyridostigmine: May improve quality of life and reduce dosing frequency from 4.3 to 3.6 times daily 7
• Recognize that myasthenia gravis associated with immune checkpoint inhibitors may be monophasic: Additional corticosteroid-sparing agents may not be required in these cases 4

Follow-up and Monitoring

• Regular pulmonary function assessment is crucial, especially for patients with generalized disease 1, 2
• Neurological follow-up to adjust treatment as needed 2
• Monitor for disease progression, as approximately 50-80% of patients with initial ocular symptoms may develop generalized myasthenia within a few years 1

Pyridostigmine has been the mainstay of symptomatic treatment for myasthenia gravis for over 50 years and is generally considered safe and effective 8. However, it typically provides only partial benefit, and most patients with moderate to severe disease will eventually require immunosuppressive therapy 8.