A 52-year-old woman presents with progressive ptosis, diplopia, and proximal muscle weakness worsening towards the end of the day. Clinical examination reveals fatigable weakness. Which investigation is most appropriate to confirm the diagnosis of myasthenia gravis?

Explanation

## Diagnosis of Myasthenia Gravis: Investigation Hierarchy **Key Point:** Serum anti-AChR antibody titre is the gold standard confirmatory test for myasthenia gravis, with high specificity (~99%) and moderate sensitivity (~80–90% in generalized MG, ~50% in ocular MG). ### Why Anti-AChR Antibodies? Myasthenia gravis is an autoimmune disorder where IgG antibodies bind to acetylcholine receptors at the neuromuscular junction, causing: - Complement-mediated destruction of the postsynaptic membrane - Blockade of acetylcholine binding - Reduced number of functional AChRs Detection of these antibodies provides **definitive serological confirmation** and correlates with disease severity. ### Investigation Comparison for NMJ Disorders | Investigation | Sensitivity (Generalized MG) | Specificity | Utility | Limitations | |---|---|---|---|---| | Anti-AChR antibody | 80–90% | ~99% | Gold standard; diagnostic | Negative in ~10–20% (seronegative MG) | | Edrophonium test | ~95% | ~90% | Bedside; rapid response | Cholinergic crisis risk; largely obsolete | | Repetitive nerve stimulation (RNS) | 60–70% | ~95% | Objective; shows decremental response | Less sensitive than antibody; requires expertise | | Single-fiber EMG (SFEMG) | ~90% | ~80% | Most sensitive; detects neuromuscular transmission defect | Non-specific; abnormal in other NMJ disorders | | Muscle biopsy | Variable | Low | Excludes myositis; rarely diagnostic for MG | Invasive; not first-line | **High-Yield:** In modern practice, **serum anti-AChR antibody testing is the first-line confirmatory investigation** because it is: - Non-invasive - Highly specific (rules in disease) - Quantifiable (correlates with severity and treatment response) - Safe (no risk of cholinergic crisis) **Clinical Pearl:** Seronegative MG (10–20% of cases) occurs when anti-AChR antibodies are absent; in these patients, anti-MuSK (muscle-specific kinase) antibodies or SFEMG may be needed for confirmation. **Tip:** The edrophonium test, though historically important, is now rarely used due to the risk of cholinergic crisis and the availability of safer serological testing.