What medication should be given to a patient with bilateral ptosis, upper and lower limbs weakness, positive Simpson test, and improved ptosis after Edrophonium (Tensilon) test?

Management of Myasthenia Gravis with Bilateral Ptosis and Limb Weakness

Pyridostigmine is the first-line medication for a patient with bilateral ptosis, upper and lower limb weakness, positive Simpson test, and improved ptosis after Edrophonium test, as these findings are diagnostic for myasthenia gravis. 1

Diagnostic Confirmation

The clinical presentation strongly suggests myasthenia gravis (MG):

• Bilateral ptosis
• Upper and lower limb weakness
• Positive Simpson test (fatigable weakness)
• Positive Edrophonium (Tensilon) test with improvement of ptosis

The Edrophonium test is particularly significant as it confirms the diagnosis by temporarily blocking acetylcholinesterase, increasing acetylcholine at the neuromuscular junction, and transiently improving symptoms 2. This test has high specificity for myasthenia gravis.

Treatment Algorithm

1. First-line treatment: Pyridostigmine

   • Starting dose: 30 mg orally three times daily 3, 1
   • Gradually increase to maximum of 120 mg orally four times daily as tolerated based on symptoms 1
   • Extended-release formulation (180 mg) may be used once or twice daily with at least 6 hours between doses 4

2. If inadequate response to pyridostigmine alone:

   • Add corticosteroids (prednisone 1-1.5 mg/kg orally daily) 3, 1
   • 66-85% of patients show positive response to corticosteroids 3

3. For moderate to severe generalized weakness (MGFA class 3-4):

   • Continue corticosteroids
   • Consider IVIG 2 g/kg IV over 5 days (0.4 g/kg/d) or plasmapheresis 3
   • Admit for monitoring if respiratory symptoms develop

Medication Considerations

• Avoid medications that can worsen myasthenia:

  • β-blockers
  • IV magnesium
  • Fluoroquinolones
  • Aminoglycosides
  • Macrolides 3, 1

• Safe alternative antibiotics if needed:

  • Penicillins
  • Cephalosporins
  • Tetracyclines 1

Monitoring and Follow-up

• Regular neurological assessments
• Monitor for signs of respiratory compromise
• Pulmonary function assessment with negative inspiratory force (NIF) and vital capacity (VC) 1
• Consider additional diagnostic tests:
  • AChR and anti-striated muscle antibodies
  • CPK, aldolase, ESR, CRP to rule out concurrent myositis 3

Pitfalls to Avoid

1. Delayed recognition of respiratory involvement: Respiratory muscle weakness can progress rapidly and requires immediate intervention.

2. Overlooking concurrent conditions: Myasthenia gravis may be associated with thymoma (10-20% of AChR-positive patients) 1.

3. Medication interactions: Many medications can exacerbate myasthenia symptoms, particularly antibiotics and cardiovascular drugs.

4. Undertreatment: Some patients require combination therapy with pyridostigmine and immunosuppression for adequate symptom control.

5. Overtreatment: Excessive dosing of pyridostigmine can paradoxically worsen symptoms (cholinergic crisis).

In conclusion, the correct answer is A. Pyridostigmine, which is the first-line treatment for myasthenia gravis based on the clinical presentation and positive Edrophonium test.