A 38-year-old woman presents with progressive ptosis, diplopia, and bulbar weakness over 3 weeks. Clinical examination reveals fatigable weakness that improves with rest. You suspect myasthenia gravis. Which investigation is most appropriate to confirm the diagnosis?

Explanation

## Investigation of Choice in Myasthenia Gravis ### Diagnostic Hierarchy **Key Point:** Serum anti-AChR antibody testing is the most specific and first-line confirmatory test for myasthenia gravis, with 80–90% sensitivity in generalized MG and 50% in ocular MG. **High-Yield:** Anti-AChR antibodies are: - Highly specific (>99%) for MG when positive - Detectable in ~80% of generalized MG and ~50% of purely ocular MG - The gold-standard serological marker - Non-invasive and widely available ### Comparison of Investigations | Investigation | Sensitivity (Generalized MG) | Sensitivity (Ocular MG) | Specificity | Invasiveness | When Used | |---|---|---|---|---|---| | Anti-AChR antibodies | 80–90% | 50% | >99% | Non-invasive | First-line confirmatory test | | Repetitive nerve stimulation | 60–70% | 10–15% | High | Electrophysiology | When serology negative, suspected seronegative MG | | Single-fiber EMG | 90–95% | 80–90% | Moderate | Needle electrode | Confirmatory in seronegative cases, research | | Brain MRI | N/A | N/A | N/A | Imaging | Rule out structural lesions, not diagnostic for MG | ### Clinical Reasoning 1. **Serology first:** Anti-AChR antibody testing is non-invasive, highly specific, and should be ordered before electrophysiological studies in suspected MG. 2. **Sensitivity in this case:** The patient has generalized MG (bulbar + ocular + limb weakness), so anti-AChR antibody sensitivity is highest (~80–90%). 3. **Confirmatory value:** A positive result confirms the diagnosis; a negative result does not exclude MG (seronegative MG exists in ~15% of generalized cases). **Clinical Pearl:** Patients with positive anti-AChR antibodies have a higher risk of thymoma (~10–15%) and should undergo chest imaging (CT or MRI) to screen for mediastinal pathology. **Tip:** If anti-AChR antibodies are negative and clinical suspicion remains high, order anti-muscle-specific kinase (MuSK) antibody testing (positive in ~40% of seronegative MG) or proceed to RNS/SFEMG. [cite:Harrison 21e Ch 378]