What is the treatment approach for a patient with suspected Myasthenia gravis?

Treatment Approach for Myasthenia Gravis

Begin with pyridostigmine 30 mg orally three times daily as first-line symptomatic treatment, 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) if symptoms persist or worsen beyond mild disease. 1, 2

Initial Diagnostic Confirmation

Before initiating treatment, confirm the diagnosis with:

• Serologic testing: Acetylcholine receptor (AChR) antibodies and antistriated muscle antibodies in blood 1, 2
• If AChR antibodies are negative: Test for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies 1, 2
• Electrodiagnostic studies: Single-fiber EMG has >90% sensitivity for ocular myasthenia, while repetitive nerve stimulation is positive in only one-third of ocular cases 2, 3
• Ice pack test: Apply ice pack over closed eyes for 2 minutes—highly specific for ocular myasthenia 2
• Pulmonary function testing: Negative inspiratory force and vital capacity, especially critical in generalized disease 1

Stepwise Treatment Algorithm

Step 1: Symptomatic Treatment (All Patients)

• Start pyridostigmine 30 mg orally three times daily 1, 2, 4
• Titrate upward gradually to maximum 120 mg orally four times daily based on tolerability and symptom control 1, 2, 3
• Note: Approximately 50% of patients with ocular myasthenia show minimal response to pyridostigmine alone and will require escalation 2, 3
• Conversion for IV use: 30 mg oral = 1 mg IV pyridostigmine or 0.75 mg neostigmine IM if oral route unavailable 1

Step 2: Immunosuppressive Therapy (Grade 2 or Higher Symptoms)

• Add prednisone 1-1.5 mg/kg orally daily if pyridostigmine provides insufficient control 1, 2, 3
• Response rate: 66-85% of patients show positive response to corticosteroids 2, 3
• Taper gradually based on symptom improvement 1, 2
• Consider early corticosteroid initiation in ocular myasthenia with persistent diplopia despite pyridostigmine 2

Step 3: Steroid-Sparing Agents (Moderate to Severe Disease)

• Azathioprine as third-line option for patients requiring long-term immunosuppression 2, 3
• Alternative agents: Mycophenolate mofetil, cyclosporine, or tacrolimus for steroid-sparing effect 5, 6, 7

Step 4: Acute Crisis Management (Grade 3-4 Exacerbations)

For myasthenic crisis with respiratory compromise or severe generalized weakness:

• Immediate hospitalization with ICU-level monitoring capability 1, 2
• IVIG 2 g/kg total dose over 5 days (0.4 g/kg/day × 5 days) OR plasmapheresis 1, 2
• Continue corticosteroids concurrently during IVIG or plasmapheresis 1
• Frequent pulmonary function monitoring: Negative inspiratory force and vital capacity 1, 2
• Daily neurologic evaluations 1
• Pyridostigmine may be continued but can be discontinued if intubation required 1

Critical distinction: IVIG is reserved for Grade 3-4 exacerbations requiring hospitalization—it should NOT be used for chronic maintenance therapy 1

Medications to Strictly Avoid

Educate all patients to avoid these medications that worsen myasthenic symptoms:

• β-blockers 1, 2, 3
• Intravenous magnesium 1, 2, 3
• Fluoroquinolone antibiotics 1, 2, 3
• Aminoglycoside antibiotics 1, 2, 3
• Macrolide antibiotics 1, 2, 3
• Metoclopramide (can trigger myasthenic crisis) 1
• Barbiturate-containing medications (e.g., butalbital) 1

Thymectomy Considerations

• Clear benefit demonstrated in AChR antibody-positive generalized MG up to age 65 years 5
• Screen for thymoma: 30-50% of patients with thymomas have myasthenia gravis 2
• Preoperative antibody testing mandatory to avoid respiratory failure during anesthesia 2

Critical Monitoring and Follow-up

• Regular pulmonary function assessment in all patients with generalized disease 1, 2, 3
• Monitor for progression: 50-80% of patients with initial ocular symptoms develop generalized myasthenia within a few years 2
• Regular neurology consultation to adjust treatment as needed 1
• Plan activities around medication timing for optimal strength 1

Important Clinical Pitfalls

• Pupillary involvement excludes myasthenia gravis—pupils are characteristically spared because MG affects nicotinic receptors at the neuromuscular junction, not autonomic innervation 2
• If pupils are abnormal, immediately consider third nerve palsy, Horner syndrome, or other neurologic causes instead 2
• Sequential therapy (TPE followed by IVIG) is no more effective than either treatment alone and should be avoided 1
• IVIG is preferred in pregnant women over plasmapheresis due to fewer monitoring requirements 1
• In resource-limited settings, plasmapheresis may be more cost-effective than IVIG, though it requires specialized equipment 1