What is the initial treatment for Myasthenia Gravis?

Initial Treatment for Myasthenia Gravis

Start pyridostigmine bromide at 30 mg orally three times daily as first-line symptomatic treatment, gradually titrating upward based on clinical response to a maximum of 120 mg four times daily. 1, 2, 3

Stepwise Treatment Algorithm

Mild Disease (Grade 2: Ocular or Mild Generalized Weakness)

First-Line: Pyridostigmine Monotherapy

• Begin pyridostigmine at 30 mg orally three times daily 4, 1, 2
• Gradually increase dose based on symptom control and tolerability 4, 1
• Maximum dosing: 120 mg orally four times daily 4, 1, 2
• This may be sufficient as monotherapy in mild disease 5

Important caveat: Approximately 50% of patients with ocular myasthenia show minimal response to pyridostigmine alone and will require escalation to corticosteroids 1

Second-Line: Add Corticosteroids

• If pyridostigmine provides insufficient control after adequate trial, add prednisone 1-1.5 mg/kg orally daily 4, 1, 2
• Corticosteroids are effective in approximately 66-85% of patients 1, 6
• Taper gradually based on symptom improvement 4, 2, 6

Moderate to Severe Disease (Grade 3-4: Severe Generalized Weakness, Dysphagia, Respiratory Involvement)

Immediate Hospitalization Required

• Admit to ICU-level monitoring for any dysphagia, facial weakness, or respiratory muscle weakness 4, 2
• Continue pyridostigmine and corticosteroids 4, 2
• Initiate IVIG 2 g/kg IV over 5 days (0.4 g/kg/day) OR plasmapheresis for 5 days 4, 1, 2
• Perform frequent pulmonary function assessment with negative inspiratory force and vital capacity monitoring 4, 2
• Daily neurologic review 4

Critical Medications to Avoid

Strictly avoid these medications that worsen myasthenic symptoms:

• β-blockers 4, 1, 2
• IV magnesium 4, 1, 2
• Fluoroquinolone antibiotics 4, 1, 2, 6
• Aminoglycoside antibiotics 4, 1, 2, 6
• Macrolide antibiotics 4, 2, 6

Essential Diagnostic Workup Before Treatment

• Acetylcholine receptor (AChR) antibodies and antistriated muscle antibodies in blood 1, 2, 6
• If AChR antibodies negative, test for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies 2, 6
• Electrodiagnostic studies with repetitive stimulation and/or jitter studies 4, 1
• Baseline pulmonary function testing (negative inspiratory force and vital capacity) 4, 2
• If respiratory insufficiency or elevated CPK/troponin, perform ECG and echocardiogram to rule out concomitant myocarditis 4

Third-Line Immunosuppressive Therapy

For patients requiring chronic immunosuppression:

• Azathioprine is the preferred steroid-sparing agent for long-term management 1, 6, 5
• Consider in patients with moderate to severe disease requiring ongoing immunosuppression 1
• Newer agents like efgartigimod alfa-fcab are available for refractory AChR-positive patients 1, 6

Common Pitfalls

IVIG is NOT for chronic maintenance therapy - Use only for acute exacerbations or crisis situations 2. The American Academy of Neurology explicitly recommends against chronic IVIG maintenance 2.

Monitor for respiratory compromise - Regular pulmonary function assessment is crucial, as 50-80% of patients with initial ocular symptoms may develop generalized myasthenia within a few years 1.

Pyridostigmine side effects - Can cause bradycardia and AV block; if this occurs, consider adding hyoscyamine (muscarinic antagonist) rather than discontinuing pyridostigmine 7.