A 28-year-old woman from Delhi presents with a 3-month history of progressive ptosis and diplopia. Symptoms worsen towards the evening and improve after rest. On examination, she has bilateral ptosis that worsens with sustained upward gaze for 30 seconds. Pupils are normal and reactive. She has mild proximal weakness of the shoulders and hips. Serum acetylcholine receptor (AChR) antibodies are positive. Chest CT shows no thymoma. Which of the following is the most appropriate initial pharmacological management?

Explanation

## Initial Management of Myasthenia Gravis **Key Point:** Pyridostigmine is the first-line symptomatic agent in seronegative and seropositive myasthenia gravis without crisis or severe systemic involvement. ### Mechanism of Action Pyridostigmine is an acetylcholinesterase inhibitor that increases acetylcholine concentration at the neuromuscular junction, improving neuromuscular transmission. It provides symptomatic relief within hours to days. ### Treatment Algorithm for MG ```mermaid flowchart TD A[Confirmed MG diagnosis]:::outcome --> B{Severity & urgency?}:::decision B -->|Mild-moderate, stable| C[Pyridostigmine]:::action B -->|Moderate-severe or crisis| D[IV immunoglobulin or Plasmapheresis]:::urgent C --> E{Adequate response?}:::decision E -->|Yes| F[Continue + monitor]:::action E -->|No| G[Add immunosuppression]:::action G --> H[Prednisolone ± Azathioprine]:::action D --> I[Followed by immunosuppression]:::action ``` ### Why Pyridostigmine First? | Feature | Pyridostigmine | Prednisolone | IVIG | |---------|---|---|---| | **Onset** | Hours to days | Weeks to months | 3–5 days | | **Use case** | Mild-moderate, stable | Moderate-severe, long-term | Crisis, rapid deterioration | | **Side effects** | Cholinergic excess (rare) | Infection, hyperglycemia | Headache, renal impairment | | **First-line?** | Yes, always | No, second-line | No, reserved for crisis | **High-Yield:** This patient has: - Seropositive MG (AChR+ antibodies) - No thymoma - Mild-to-moderate symptoms (ocular + mild systemic) - Stable presentation (no respiratory compromise, no crisis) Pyridostigmine is the standard first-line agent. Immunosuppression (prednisolone or azathioprine) is added only if pyridostigmine alone is insufficient. **Clinical Pearl:** Always check for cholinergic crisis (bronchospasm, bradycardia, muscle fasciculations) when starting or escalating pyridostigmine; however, this is rare at therapeutic doses. [cite:Harrison 21e Ch 382]