Initial Workup and Treatment for Myasthenia Gravis
The initial workup for myasthenia gravis should include a complete rheumatologic and neurologic history and examination, blood tests for muscle inflammation, and specific diagnostic tests including anti-acetylcholine receptor antibodies, while first-line treatment is pyridostigmine bromide. 1, 2, 3
Diagnostic Workup
Clinical Assessment
- Complete rheumatologic and neurologic history focusing on:
- Pattern of muscle weakness (typically worse with exertion, improves with rest)
- Distribution of weakness (ocular, bulbar, limb muscles)
- Fluctuating nature of symptoms
- Thorough neurologic examination including muscle strength testing
- Examination of skin for findings suggestive of dermatomyositis
Laboratory Testing
- Anti-acetylcholine receptor (AChR) antibody titers
- Muscle inflammation markers:
- Creatine kinase (CK)
- Transaminases (AST, ALT)
- Lactate dehydrogenase (LDH)
- Aldolase
- Inflammatory markers (ESR, CRP)
- Troponin to evaluate myocardial involvement
Specialized Testing
- Ice pack test (highly specific for ocular myasthenia)
- Edrophonium (Tensilon) test (95% sensitive for generalized MG, 86% for ocular MG)
- Caution: carries risks including bradycardia, bronchospasm, and hypotension 2
- Electrophysiologic testing:
- Repetitive nerve stimulation (shows decremental response)
- Single-fiber electromyography (SFEMG) - gold standard with >90% sensitivity for ocular MG 2
- Consider imaging (MRI) when diagnosis is uncertain
- Consider paraneoplastic autoantibody testing 1
- Chest imaging to evaluate for thymoma
Treatment Algorithm
Step 1: Symptomatic Treatment
- First-line: Pyridostigmine bromide (acetylcholinesterase inhibitor) 2, 3
- Starting dose: 30 mg orally three times daily
- Gradually increase to maximum of 120 mg orally four times daily based on symptom response
Step 2: For Mild Generalized or Persistent Symptoms
- Corticosteroids: Prednisone 0.5-1 mg/kg orally daily 1, 2
- Approximately 66-85% of patients show positive response
- Initiate steroid-sparing agent concurrently to minimize steroid exposure:
- Methotrexate 15 mg weekly, OR
- Azathioprine 2 mg/kg of ideal body weight in divided doses, OR
- Mycophenolate mofetil 500 mg twice daily increasing to 1000 mg twice daily 2
Step 3: For Severe Symptoms or Myasthenic Crisis
- Plasmapheresis: First-line for acute phase, particularly with respiratory compromise 2
- IVIG: Alternative when plasmapheresis is unavailable or contraindicated 2
- Corticosteroids: Prednisone 0.5-1.5 mg/kg orally daily 2
Step 4: Consider Thymectomy
- Recommended for patients with generalized disease, especially those with detectable AChR antibodies
- Mandatory for all patients with suspected thymoma 4, 5
Monitoring and Precautions
Regular Monitoring
- Baseline assessment of MG symptoms and severity
- Daily neurological assessments when starting or adjusting medications
- Regular pulmonary function testing in moderate to severe cases 2
Medications to Avoid
- Daptomycin
- Aminoglycosides
- β-blockers
- IV magnesium
- Fluoroquinolones
- Macrolides 2
Safer Alternative Medications
- Penicillins
- Cephalosporins
- Tetracyclines (including tigecycline) 2
Special Considerations
For Elderly Patients
- Start at lower doses and titrate more slowly
- Increased sensitivity to side effects 2
For Surgical Patients
- Continue pyridostigmine until surgery
- May affect response to neuromuscular blocking agents 2
Treatment Response
- Most patients can achieve remission or significant improvement with appropriate therapy
- Some treatments entail significant side effects and considerable cost 4
- Regular follow-up is essential to monitor disease activity and medication side effects