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

Diagnostic Criteria and Treatment Options for Myasthenia Gravis (MG)

The diagnosis of Myasthenia Gravis requires specific antibody testing (primarily acetylcholine receptor antibodies), electrodiagnostic studies, and clinical evaluation of fatigable muscle weakness, while treatment should follow a stepwise approach starting with pyridostigmine and potentially escalating to immunosuppressive therapy based on disease severity. 1

Diagnostic Criteria

Clinical Presentation

• Fatigable or fluctuating muscle weakness, generally more proximal than distal 1
• Ocular and/or bulbar involvement (ptosis, extraocular movement abnormalities resulting in double vision, dysphagia, dysarthria, facial muscle weakness) 1
• Possible neck and/or respiratory muscle weakness 1
• May occur with myositis and/or myocarditis 1

Diagnostic Testing Algorithm

Laboratory Testing

• Acetylcholine receptor (AChR) and antistriated muscle antibodies in blood 1
• If AChR antibodies are negative, test for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies 1
• Creatine phosphokinase (CPK), aldolase, ESR, and CRP to evaluate for possible concurrent myositis 1
• If respiratory insufficiency or elevated CPK/troponin T, perform cardiac examination with ECG and transthoracic echocardiogram to rule out concomitant myocarditis 1

Bedside Tests

• Ice test: application of an ice pack over closed eyes for 2 minutes (ptosis) or 5 minutes (strabismus) to demonstrate reduction of symptoms - highly specific for MG 1
• Rest test without ice pack can also aid in diagnosis 1
• Edrophonium (Tensilon) test:
  • For adults: 2 mg IV initially, followed by remaining 8 mg if no reaction occurs after 45 seconds 2
  • Must be performed in a monitored setting with atropine available due to risk of muscarinic side effects 1
  • 95% sensitive for generalized myasthenia and 86% sensitive for ocular myasthenia 1

Neurophysiologic Testing

• Electrodiagnostic studies, including neuromuscular junction testing with repetitive stimulation and/or jitter studies 1
• Nerve conduction study (NCS) to exclude neuropathy 1
• Needle EMG to evaluate for myositis 1
• Single-fiber electromyography (positive in over 90% of patients with ocular myasthenia) - considered the gold standard for diagnosis in many centers 1

Imaging

• Consider MRI of brain and/or spine depending on symptoms to rule out CNS involvement or alternative diagnoses 1
• Chest imaging to evaluate for thymoma, particularly in patients with generalized MG 1

Pulmonary Function Assessment

• Negative inspiratory force and vital capacity measurements 1
• Critical for monitoring risk of respiratory compromise 1

Treatment Options

Grading System

Treatment is based on the Myasthenia Gravis Foundation of America (MGFA) classification system 1:

• Grade 1: Ocular symptoms and findings only
• Grade 2: Mild generalized weakness
• Grades 3-4: Moderate to severe generalized weakness
• Grade 5: Myasthenic crisis requiring intubation

First-Line Treatment

• Pyridostigmine (acetylcholinesterase inhibitor):
  • Starting at 30 mg orally three times daily 1
  • Gradually increase to maximum of 120 mg orally four times daily as tolerated 1
  • Note: About 50% of patients with strabismus-associated myasthenia show minimal response 1

Second-Line Treatment

• Corticosteroids (for Grade 2 or higher symptoms):
  • Prednisone 1-1.5 mg/kg orally daily 1
  • Approximately 66-85% of patients show positive response 1
  • Wean based on symptom improvement 1

Third-Line/Advanced Treatment Options

• For moderate to severe disease (Grades 3-4):
  • IVIG: 2 g/kg IV over 5 days (0.4 g/kg/day) 1
  • OR Plasmapheresis for 5 days 1
  • Immunosuppressive therapy with azathioprine 1
  • Newer FDA-approved therapies for AChR-antibody positive patients: eculizumab, efgartigimod, and ravulizumab 3
  • Rituximab may be beneficial, especially for MuSK-positive MG 3
  • Thymectomy: indicated in all cases with thymoma and beneficial in selected patients with non-thymomatous MG 1, 3

Management of Myasthenic Crisis

• Admit patient, may need ICU-level monitoring 1
• Neurology consultation 1
• Corticosteroids plus IVIG or plasmapheresis 1
• Frequent pulmonary function assessment 1
• Daily neurologic evaluation 1

Important Considerations and Pitfalls

Medications to Avoid

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

Special Considerations

• ICPi-associated myasthenia gravis may be monophasic; additional corticosteroid-sparing agents may not be required 1
• Surgical management for strabismus should only be considered after disease stabilization (typically 2-3 years after treatment initiation) 1
• Care is needed with anesthetic agents in patients with respiratory muscle weakness 1
• Diagnosis and management require collaboration between an experienced ophthalmologist and neurologist 1

Disease Monitoring

• Regular pulmonary function assessment in patients with generalized MG 1
• Monitor for concurrent autonomic dysfunction 1
• Assess treatment response using validated outcome measures 4