What are the symptoms and treatment options for Myasthenia Gravis (MG)?

Myasthenia Gravis: Symptoms and Treatment Options

Myasthenia gravis (MG) is characterized by fluctuating muscle weakness that worsens with activity and improves with rest, with primary treatment consisting of pyridostigmine as first-line therapy, followed by corticosteroids and steroid-sparing agents for more severe disease. 1, 2

Clinical Presentation

Common Symptoms

• Ocular symptoms (often initial presentation):

  • Ptosis (drooping eyelids)
  • Diplopia (double vision)
  • External ophthalmoplegia 1, 3, 4

• Bulbar symptoms:

  • Dysphonia (voice weakness) 5
  • Dysphagia (difficulty swallowing)
  • Slurred speech 6

• Limb and axial muscle involvement:

  • Fatigable weakness
  • Worsening with continued use
  • Improvement with rest 7

Important Clinical Patterns

• Symptoms typically worsen throughout the day or with prolonged activity
• Weakness may be asymmetric
• Respiratory muscle involvement can lead to respiratory insufficiency in severe cases 1
• Symptoms worsen during intercurrent infections, fever, and physical/emotional exhaustion 6

Diagnostic Approach

Clinical Tests

• Ice pack test: Application of ice to affected muscles (particularly ptotic eyelids) may temporarily improve symptoms
• Edrophonium (Tensilon) test: Rapid, temporary improvement in muscle strength after administration 1

Laboratory and Electrodiagnostic Tests

• Acetylcholine receptor (AChR) antibodies: Positive in most patients with generalized MG
• Anti-MuSK antibodies: May be positive in AChR-negative patients
• Electrodiagnostic studies:
  • Repetitive nerve stimulation: Shows decremental response
  • Single-fiber EMG: Gold standard with >90% sensitivity, especially for ocular MG 1

Imaging

• Chest imaging (CT/MRI): To evaluate for thymoma (present in some MG patients) 1

Treatment Algorithm

First-Line Treatment

• Pyridostigmine (acetylcholinesterase inhibitor):
  • Starting dose: 30 mg orally three times daily
  • Can be gradually increased to maximum of 120 mg four times daily
  • Maximum daily dose up to 600 mg based on symptoms 1, 2

For Inadequate Response to Pyridostigmine

• Corticosteroids:

  • Prednisone 0.5-1.5 mg/kg orally daily
  • Important: Must increase dose slowly to avoid precipitating myasthenic crisis
  • Positive response rate: 66-85% 1, 3

• Steroid-sparing agents (initiated concurrently with corticosteroids):

  • Methotrexate: 15 mg weekly
  • Azathioprine: 2 mg/kg of ideal body weight in divided doses
  • Mycophenolate mofetil: Start at 500 mg twice daily, increase to 1000 mg twice daily 1, 3

For Myasthenic Crisis

• Hospital admission and ICU monitoring
• IVIG: 2 g/kg over 5 days OR
• Plasmapheresis: For 5 days 1

Surgical Management

• Thymectomy:
  • Indicated for all patients with thymoma
  • May reduce symptoms in AChR antibody-positive generalized MG up to age 65
  • Remission rates approximately 11.6% after thymectomy 1

Monitoring

• Respiratory function:
  • Negative inspiratory force (NIF)
  • Vital capacity (VC)
  • NIF > -60 cm H₂O: Continued routine monitoring
  • NIF -20 to -60 cm H₂O: Close monitoring and potential intervention 1

Important Precautions

Medications to Avoid

• β-blockers
• IV magnesium
• Fluoroquinolones
• Aminoglycosides
• Macrolides 1

Anesthetic Considerations

• Safe anesthetics: Propofol, sevoflurane, isoflurane, fentanyl, remifentanil, lidocaine, bupivacaine
• Avoid: Atracurium, mivacurium, succinylcholine
• Preferred neuromuscular blocker: Rocuronium (can be antagonized with sugammadex) 1

Special Considerations

• Ocular MG: May remain limited to ocular muscles or progress to generalized MG within first two years 3, 4
• Laryngeal MG: Rare presentation with dysphonia as primary symptom, often misdiagnosed 5
• Trigger factors: Respiratory infections (bacterial or viral) are the most common triggers for exacerbations 6