A 32-year-old woman from Delhi presents with a 3-month history of progressive ptosis and diplopia. She reports that symptoms worsen toward the end of the day and improve after rest. On examination, she has bilateral ptosis that worsens with sustained upward gaze for 30 seconds (fatigability). Pupillary reflexes are normal. She has no sensory or motor weakness in the limbs. Serum anti-acetylcholine receptor (AChR) antibodies are positive. What is the most appropriate next step in management?

Explanation

## Clinical Diagnosis and Management **Key Point:** This patient has seropositive myasthenia gravis (MG) with ocular predominance. The diagnosis is confirmed by positive anti-AChR antibodies and characteristic fatigability on examination. ### Management Strategy for Seropositive MG **High-Yield:** First-line pharmacological management of MG is acetylcholinesterase inhibitors (pyridostigmine), which increase acetylcholine availability at the neuromuscular junction. **Clinical Pearl:** In seropositive MG, thymectomy has a 80–90% remission rate and should be offered to all patients aged 15–60 years, even if asymptomatic on medication. This patient is an ideal candidate. ### Treatment Algorithm ```mermaid flowchart TD A[Confirmed MG with AChR antibodies]:::outcome --> B[Start acetylcholinesterase inhibitor]:::action B --> C[Pyridostigmine 60 mg TDS]:::action C --> D{Age 15-60 and fit for surgery?}:::decision D -->|Yes| E[Refer for thymectomy]:::action D -->|No| F[Continue medical management] E --> G[Thymectomy + continue pyridostigmine]:::action G --> H[Monitor for remission/improvement]:::outcome ``` **Mnemonic:** **STEP** for MG management: - **S**tart acetylcholinesterase inhibitors (pyridostigmine) - **T**hymectomy (in seropositive, age 15–60) - **E**xamine for thymoma (CT chest) - **P**rednisone/immunosuppressants if inadequate response ### Why Pyridostigmine First? 1. **Mechanism:** Inhibits acetylcholinesterase, prolonging acetylcholine half-life at the neuromuscular junction. 2. **Onset:** Rapid symptomatic relief (30–60 minutes). 3. **Safety:** Well-tolerated; no immunosuppression needed initially. 4. **Efficacy:** Adequate in ~30% of ocular MG; combined with thymectomy, remission rates improve significantly. **Dosing:** Pyridostigmine 60 mg three times daily (or 30 mg if GI side effects occur); maximum 120 mg per dose. ### Thymectomy Indication - Seropositive MG, age 15–60 years → **thymectomy is standard of care** - Even without thymoma, 80–90% achieve remission or significant improvement - Should be performed after stabilization on pyridostigmine - CT chest must be done preoperatively to exclude thymoma [cite:Harrison 21e Ch 382] ## Why Other Options Are Incorrect **IVIG and plasmapheresis** are reserved for: - Myasthenic crisis (respiratory failure) - Acute exacerbation unresponsive to standard therapy - Preoperative optimization in urgent thymectomy This patient is stable and does not require these aggressive interventions. **Edrophonium test** is now rarely used due to: - Risk of cholinergic crisis - Availability of reliable serological testing (anti-AChR antibodies) - Availability of single-fiber electromyography (SFEMG) for seronegative cases