What is the treatment for myasthenia gravis?

Treatment of Myasthenia Gravis

Start with pyridostigmine 30 mg orally three times daily as first-line symptomatic therapy, titrating up to a maximum of 120 mg four times daily based on clinical response, and escalate to corticosteroids (prednisone 1-1.5 mg/kg daily) for Grade 2 or higher symptoms that persist despite optimal pyridostigmine dosing. 1, 2, 3

Stepwise Treatment Algorithm

Initial Symptomatic Management

• Begin pyridostigmine at 30 mg orally three times daily and gradually increase based on tolerability and symptom control, with maximum dosing of 120 mg orally four times daily 1, 2, 4
• This acetylcholinesterase inhibitor is FDA-approved for myasthenia gravis and provides symptomatic relief by increasing acetylcholine availability at the neuromuscular junction 3, 5
• Note that approximately 50% of patients, particularly those with ocular myasthenia, may show minimal response to pyridostigmine alone and will require escalation to immunosuppressive therapy 1, 4

Escalation to Immunosuppressive Therapy

For Grade 2 symptoms (mild generalized weakness):

• Add corticosteroids directly if pyridostigmine provides insufficient control 6, 2
• Start prednisone 1-1.5 mg/kg orally daily 6, 2
• Taper gradually based on symptom improvement 6, 2
• Approximately 66-85% of patients show positive response to corticosteroids 1, 4

For Grade 3-4 symptoms (severe generalized weakness or myasthenic crisis):

• Permanently discontinue immune checkpoint inhibitors if applicable, and immediately hospitalize with ICU-level monitoring capability 6, 2
• Initiate IVIG 2 g/kg total dose over 5 days (administered as 0.4 g/kg/day for 5 consecutive days) OR plasmapheresis for 5 days 6, 2, 4
• Continue corticosteroids concurrently during IVIG or plasmapheresis 6, 2
• Perform frequent pulmonary function assessments with negative inspiratory force and vital capacity monitoring 6, 2, 4
• Conduct daily neurologic evaluations 6, 2

Long-term Steroid-Sparing Options

• Consider azathioprine as third-line immunosuppressive therapy for moderate to severe disease requiring steroid-sparing agents 1, 4
• Thymectomy is indicated in all cases with thymoma and may substantially reduce symptoms in certain subpopulations, particularly early-onset generalized MG 4, 5
• Newer biologics including complement inhibitors (eculizumab, ravulizumab) and FcRn inhibitors (efgartigimod alfa-fcab) are FDA-approved for anti-AChR antibody-positive patients who remain symptomatic despite standard therapy 4, 7

Critical Medications to Avoid

Strictly educate patients to avoid the following medications that can precipitate myasthenic crisis:

• β-blockers 6, 2, 4
• Intravenous magnesium 6, 2, 4
• Fluoroquinolone antibodies 6, 2, 4
• Aminoglycoside antibodies 6, 2, 4
• Macrolide antibodies 6, 2, 4

Essential Diagnostic Workup Before Treatment

• Measure acetylcholine receptor (AChR) and antistriated muscle antibodies in blood 6, 1, 4
• If AChR antibodies are negative, test for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies 6, 1, 4
• Perform electrodiagnostic studies including repetitive nerve stimulation and/or single-fiber EMG (>90% sensitivity in ocular MG) 1, 4
• Obtain baseline pulmonary function testing with negative inspiratory force and vital capacity 6, 4
• Check creatine phosphokinase, aldolase, ESR, and CRP to evaluate for possible concurrent myositis 6

Important Clinical Pitfalls

IVIG is NOT indicated for chronic maintenance therapy in myasthenia gravis - it should be reserved exclusively for acute exacerbations (Grade 3-4) or myasthenic crisis requiring hospitalization 2. The American Academy of Neurology explicitly recommends against chronic IVIG maintenance 2.

Monitor for disease progression: 50-80% of patients who initially present with purely ocular symptoms will progress to generalized myasthenia gravis within a few years, requiring regular pulmonary function assessment and neurologic follow-up 1, 4.

Preoperative antibody testing is mandatory: Any patient with suspected myasthenia gravis requiring surgery must have serum anti-acetylcholine receptor antibody levels measured preoperatively to avoid respiratory failure during anesthesia 1.

Monitoring and Follow-up

• Plan regular neurology consultation to adjust treatment as needed 2
• For patients with generalized disease, perform frequent pulmonary function assessments 6, 2, 4
• Instruct patients to seek immediate medical attention for significant increase in muscle weakness, changes in speech or swallowing, or respiratory difficulties 2
• Remission or stabilization is often possible after 2-3 years of treatment 4