What is myasthenia gravis?

Myasthenia Gravis

Myasthenia gravis is an autoimmune disease characterized by fatigable muscle weakness due to dysfunction at the neuromuscular junction, primarily affecting ocular and bulbar muscles first, with antibodies targeting acetylcholine receptors in approximately 80-85% of cases. 1

Clinical Presentation

Myasthenia gravis presents with distinctive patterns of muscle weakness:

• Ocular symptoms (first presentation in 50% of patients):

  • Ptosis (drooping eyelids) that worsens with fatigue
  • Diplopia (double vision)
  • Cogan lid-twitch sign (twitching when looking down then up)
  • Slow ocular saccades 2

• Bulbar symptoms:

  • Dysarthria (slurred speech)
  • Dysphagia (difficulty swallowing)
  • Facial muscle weakness 1

• Other manifestations:

  • Proximal limb weakness more than distal
  • Neck muscle weakness
  • Respiratory muscle weakness (in severe cases)
  • Fatigability that worsens throughout the day 2, 1

Diagnostic Approach

Clinical Tests

• Ice pack test: Application of ice over closed eyes for 2-5 minutes may reduce ptosis and ocular misalignment (highly specific) 2
• Rest test: Improvement of symptoms after a period of rest 2

Laboratory Tests

• Antibody testing:
  • Anti-acetylcholine receptor (AChR) antibodies (positive in 80-85% of patients)
  • Anti-muscle-specific kinase (MuSK) antibodies (5-8% of patients)
  • Anti-lipoprotein-related protein 4 (LRP4) antibodies (<1% of patients)
  • Approximately 10% remain seronegative 1, 3

Electrophysiological Tests

• Single-fiber electromyography: Considered the gold standard (>90% sensitive in ocular myasthenia) 2
• Repetitive nerve stimulation: Positive in only one-third of ocular myasthenia cases 2

Other Tests

• Tensilon (edrophonium) test: 95% sensitive for generalized myasthenia, 86% for ocular myasthenia
  • Caution: Must be performed in a monitored setting with atropine available due to risk of muscarinic side effects 2

Disease Classification

Myasthenia gravis can be classified into several subtypes:

• Ocular MG: Limited to extraocular muscles (15% of patients)
• Generalized MG: Involves multiple muscle groups (85% of patients)
• Early-onset MG: More common in younger females
• Late-onset MG: More common in older males
• Thymoma-associated MG: 10-20% of AChR-positive patients have thymoma 1, 3

Treatment

First-Line Therapy

• Acetylcholinesterase inhibitors:
  • Pyridostigmine bromide: Starting at 30 mg orally three times daily, gradually increasing to maximum of 120 mg four times daily 2, 1
  • Note: About half of patients with ocular myasthenia show minimal response 2

Immunosuppressive Therapy

• Corticosteroids: 66-85% of patients show positive response 2

  • Caution: May initially worsen symptoms 1

• Steroid-sparing agents:

  • Azathioprine (proven effective)
  • Mycophenolate
  • Newer agents: Efgartigimod alfa-fcab (FDA approved for anti-AChR positive patients) 2, 1

Surgical Management

• Thymectomy:
  • Indicated in all cases of thymoma
  • May substantially reduce symptoms in certain subpopulations 2, 1

Management of Ocular Symptoms

• Diplopia and strabismus are highly variable and often not easily managed with prisms
• Surgical intervention for strabismus may be considered after 2-3 years of disease stabilization 2

Special Considerations

• Respiratory function: Regular assessment is critical as respiratory compromise can occur 1
• Anesthesia: Special care needed with anesthetic agents in patients with respiratory muscle weakness 2
• Medications to avoid: β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolides can worsen symptoms 1
• Immune checkpoint inhibitor therapy: Can cause a rare but potentially fatal overlap syndrome with features of both myasthenia gravis and myositis 1

Multidisciplinary Management

Diagnosis and management of myasthenia gravis require collaboration between:

• Ophthalmologist (for ocular symptoms)
• Neurologist or neuro-ophthalmologist
• General surgeon (in cases requiring thymectomy) 2

Proper diagnosis and treatment significantly improve prognosis and quality of life for patients with myasthenia gravis, with most patients able to lead normal or near-normal lives with appropriate management.