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

Diagnostic Criteria and Treatment Options for Myasthenia Gravis

The diagnosis of myasthenia gravis requires antibody testing (primarily acetylcholine receptor antibodies), electrodiagnostic studies, and pulmonary function assessment, while treatment follows a stepwise approach starting with pyridostigmine and escalating to immunosuppression based on disease severity. 1

Diagnostic Criteria

Essential Diagnostic Tests

• Antibody Testing:

  • Acetylcholine receptor (AChR) antibodies - primary test 1, 2
  • If AChR antibodies are negative, test for:
    • Muscle-specific kinase (MuSK) antibodies
    • Lipoprotein-related protein 4 (LRP4) antibodies 1, 2
  • Anti-striated muscle antibodies (especially important to screen for thymoma) 1

• Electrodiagnostic Studies:

  • Neuromuscular junction testing with repetitive stimulation
  • Jitter studies
  • Nerve conduction studies to exclude neuropathy
  • Needle EMG to evaluate for concurrent myositis 1, 3

• Pulmonary Function Assessment:

  • Negative inspiratory force (NIF)
  • Vital capacity (VC) 1

Additional Diagnostic Workup

• Creatine phosphokinase (CPK), aldolase, ESR, CRP to evaluate for concurrent myositis
• Cardiac evaluation if respiratory insufficiency or elevated CPK/troponin T:
  • ECG
  • Transthoracic echocardiogram (TTE) 1
• MRI of brain and/or spine depending on symptoms to rule out CNS involvement
• Neurology consultation 1

Clinical Classification

Myasthenia gravis is classified based on:

1. Distribution of weakness:

   • Ocular MG (15% of cases): limited to extraocular muscles causing ptosis and diplopia
   • Generalized MG (85% of cases): involves multiple muscle groups 4

2. Severity grading (per Myasthenia Gravis Foundation of America):

   • Grade 2: Some symptoms interfering with activities of daily living
   • Grade 3-4: Limiting self-care, dysphagia, facial weakness, respiratory muscle weakness 1, 4

Treatment Algorithm

First-Line Treatment

• Pyridostigmine (acetylcholinesterase inhibitor):
  • FDA-approved for treatment of myasthenia gravis 5
  • Starting dose: 30 mg PO three times daily
  • Gradually increase to maximum of 120 mg orally four times daily as tolerated 1

Second-Line Treatment (Grade 2 MG)

• Corticosteroids:
  • Prednisone 1-1.5 mg/kg PO daily
  • Wean based on symptom improvement 1
• Consider continuing pyridostigmine alongside corticosteroids

Treatment for Severe Disease (Grade 3-4)

1. Hospital admission (may need ICU-level monitoring)
2. Neurology consultation
3. Corticosteroids plus one of:
   • IVIG: 2 g/kg over 5 days (0.4 g/kg/day)
   • Plasmapheresis for 5 days 1
4. Frequent monitoring:
   • Pulmonary function assessment
   • Daily neurologic evaluation 1

Surgical Management

• Thymectomy should be considered, especially in patients with thymoma (present in approximately 20% of patients) 6

Important Precautions and Pitfalls

• Avoid medications that can worsen myasthenia:

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

• Monitor for respiratory compromise:

  • All grades of myasthenia gravis warrant thorough workup and intervention
  • Respiratory failure represents the most serious complication 1, 6

• Watch for myasthenic crisis:

  • Characterized by rapid worsening of symptoms
  • Requires immediate hospitalization and intensive care 1, 7

• Consider comorbidities:

  • Thyroid disease (particularly hyperthyroidism and Hashimoto's)
  • Other autoimmune conditions 2, 6

The management of myasthenia gravis should aim for clinical remission or minimal symptoms with near-normal function and quality of life 6. Early diagnosis and appropriate treatment significantly improve outcomes and reduce morbidity and mortality associated with this condition.