What is the approach to managing myasthenia gravis?

Approach to Myasthenia Gravis: Assessment and Management

Pyridostigmine bromide administered orally two to four times a day is the first-line treatment for myasthenia gravis, though about half of patients with strabismus-associated myasthenia show minimal response. 1, 2

Diagnosis

• Fatigable or fluctuating muscle weakness, more proximal than distal, is the hallmark clinical presentation of myasthenia gravis (MG) 3
• Ocular symptoms (ptosis, diplopia) are the most common presenting features, with approximately 80% of patients presenting with ocular MG eventually developing generalized weakness 4
• Diagnostic testing should include:
  • Acetylcholine receptor (AChR) antibodies (note that about one-third of seronegative patients will be positive for muscle-specific kinase antibodies) 5, 2
  • Ice test: applying an ice pack over closed eyes for 2-5 minutes is highly specific for MG, particularly for ocular symptoms 1, 2
  • Electrodiagnostic studies: repetitive nerve stimulation (positive in only one-third of ocular MG) and single fiber electromyography (positive in over 90% of ocular MG) 5

Treatment Algorithm

First-Line Treatment

• Acetylcholinesterase inhibitors: Pyridostigmine 30-60mg orally 2-4 times daily (maximum 120mg four times daily) 1, 2, 6
• Monitor for cholinergic side effects (increased secretions, abdominal cramps, diarrhea) 6
• Be vigilant for cholinergic crisis, which requires prompt withdrawal of pyridostigmine and may require atropine administration 6

Second-Line Treatment

• If inadequate response to pyridostigmine (common in about 50% of patients with ocular symptoms):
• Corticosteroids: 66-85% of patients show positive response 5, 1
• Start at low dose and gradually increase to avoid precipitating myasthenic crisis 7
• Once symptoms are controlled, taper to lowest effective dose 7

Third-Line/Adjunctive Treatments

• Immunosuppressive therapy with azathioprine as a steroid-sparing agent 1, 3
• Other immunosuppressants such as mycophenolate mofetil may be considered 8, 7
• For refractory cases, consider:
  • Rituximab 8
  • Efgartigimod alfa-fcab 1
  • High-dose cyclophosphamide 8
  • Eculizumab 8

Surgical Options

• Thymectomy is indicated in:
  • All cases with thymoma 5, 3
  • Patients with AChR antibody-positive generalized MG (up to age 65) 3
• Strabismus surgery may be considered after disease stabilization (typically 2-3 years of treatment) if diplopia persists 5, 1

Management of Ocular Symptoms

• Diplopia and strabismus are highly variable and often not readily remedied with prisms 5, 1
• Temporary relief of ocular misalignment may be achieved with ice pack application over closed eyes for 5 minutes 1
• For persistent ptosis, consider:
  • Topical agents as additional therapy for mild/moderate ptosis 7
  • Occlusive devices, prisms, eyelid supports in stable cases 7

Management of Myasthenic Crisis

• Characterized by increasing muscle weakness involving respiratory muscles 6
• Requires:
  • Immediate respiratory support if needed 4
  • Intravenous immunoglobulin or plasmapheresis (if available) 9
  • In resource-limited settings, continuous intravenous infusion of pyridostigmine or neostigmine may be considered, though with caution due to potential cardiac arrhythmias and pneumonia 9

Special Considerations

• Avoid medications that can exacerbate MG symptoms: β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolides 2
• Regularly monitor respiratory function, especially in patients with generalized MG 2, 4
• Differentiate between myasthenic crisis (worsening disease requiring more intensive therapy) and cholinergic crisis (overdosage requiring withdrawal of anticholinesterase drugs) 6
• Fatigue is common in MG and should be managed with physical therapy with or without psychological support 3
• Management requires collaboration between an experienced ophthalmologist and neurologist 5, 2

Prognosis

• Despite available treatments, up to 20% of patients will experience a myasthenic crisis requiring ventilatory support at some point 4
• Remission or stabilization of disease is often possible after 2-3 years of treatment 5