How to manage fatigue and nystagmus in patients with myasthenia gravis?

Management of Fatigue and Nystagmus in Myasthenia Gravis

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

First-Line Treatment

• Acetylcholinesterase inhibitors: Pyridostigmine (60mg orally 2-4 times daily) is the initial symptomatic treatment for fatigue and ocular manifestations including nystagmus 1, 2
• Monitor for clinical response; dosing should be adjusted based on symptom control rather than plasma concentrations 3
• Be vigilant for signs of cholinergic crisis (increasing muscle weakness, respiratory involvement) which can be life-threatening and requires immediate discontinuation of cholinesterase inhibitors 2

Second-Line Treatment

• Corticosteroids: If pyridostigmine provides inadequate relief, corticosteroids should be added, with 66-85% of patients showing positive response 1
• Particularly beneficial for ocular symptoms that fail to respond to symptomatic treatment 4
• Start at moderate doses and taper to the minimum effective dose to minimize side effects 4

Third-Line/Adjunctive Treatments

• Immunosuppressive therapy: Consider adding azathioprine for patients with inadequate response to corticosteroids or those who need steroid-sparing agents 1, 4
• Other immunosuppressants: Cyclosporine, cyclophosphamide, methotrexate, mycophenolate mofetil may be considered in refractory cases 5
• Newer targeted therapies: Efgartigimod alfa-fcab (FDA approved for anti-acetylcholine receptor positive patients) can be considered for refractory cases 1, 6

Management of Persistent Ocular Symptoms

• Diplopia management: Ocular symptoms like nystagmus and diplopia are highly variable and often not readily remedied with prisms 1
• Rest periods: Schedule regular rest periods throughout the day to minimize fatigue-induced worsening of symptoms 4
• Ice pack application: For acute exacerbation of ocular symptoms, application of ice pack over closed eyes for 5 minutes may temporarily reduce misalignment 1

Surgical Options

• Thymectomy: Consider in patients with thymoma or in certain subpopulations with generalized MG to reduce symptoms 1, 4
• Strabismus surgery: May be considered after disease stabilization (typically 2-3 years of treatment) if diplopia persists and is not manageable with prisms 1
• Surgical management has shown modest success in cases with stabilized primary deviation that is exacerbated by fatigue 1

Multidisciplinary Approach

• Coordinated care: Management requires collaboration between ophthalmologist and neurologist 1
• Physical therapy: Consider for management of fatigue symptoms 4
• Respiratory physiotherapy: May be beneficial for patients with dysfunctional breathing 4

Special Considerations

• Monitoring for generalization: Be vigilant for signs of respiratory distress that might indicate generalization of the disease 1
• Fatigue management: Distinguish between fatigable weakness (characteristic of MG) and general fatigue, which may require different management approaches 4
• Refractory cases: For treatment-resistant cases, consider rituximab, high-dose cyclophosphamide, or eculizumab 7, 6

Common Pitfalls

• Misdiagnosis of crisis: Failure to differentiate between myasthenic crisis (requiring increased anticholinesterase therapy) and cholinergic crisis (requiring withdrawal of these medications) can have grave consequences 2
• Masking symptoms: Use of atropine to manage muscarinic side effects can mask signs of overdosage and inadvertently induce cholinergic crisis 2
• Inadequate monitoring: Failure to regularly assess for disease progression from ocular to generalized MG 1