A 35-year-old man with a history of small-cell lung cancer presents with progressive proximal muscle weakness and autonomic dysfunction. Clinical examination reveals reduced tendon reflexes. Which investigation would best demonstrate the presynaptic defect characteristic of Lambert-Eaton myasthenic syndrome (LEMS)?

Explanation

## Lambert-Eaton Myasthenic Syndrome: Electrophysiological Diagnosis **Key Point:** Repetitive nerve stimulation (RNS) showing **incremental response (post-tetanic potentiation)** is the most specific electrophysiological test for LEMS, directly demonstrating the presynaptic calcium channel dysfunction. ### Pathophysiology of LEMS LEMS is caused by autoimmune antibodies against **voltage-gated calcium channels (VGCCs)** at the presynaptic terminal, resulting in: - Reduced calcium influx during depolarization - Decreased acetylcholine (ACh) release per action potential - **Low baseline compound muscle action potential (CMAP) amplitude** - **Incremental response after high-frequency stimulation or post-tetanic potentiation** (calcium accumulates, partially restoring ACh release) ### Why RNS with Post-Tetanic Potentiation? In LEMS: 1. **Baseline RNS** shows **decremental response** (similar to MG, but less pronounced) 2. **After 10 seconds of high-frequency stimulation (50 Hz)** or **post-tetanic potentiation**, CMAP amplitude **increases by >100%** (pathognomonic for LEMS) 3. This incremental response reflects temporary restoration of calcium-dependent ACh release This pattern is **virtually diagnostic** of presynaptic dysfunction and distinguishes LEMS from myasthenia gravis. ### Investigation Comparison: LEMS vs. MG | Feature | LEMS (Presynaptic) | Myasthenia Gravis (Postsynaptic) | |---|---|---| | **RNS pattern** | Decremental at baseline; **incremental after high-frequency stimulation** | Decremental throughout | | **Post-tetanic potentiation** | **Marked increase (>100%)** | Absent or minimal | | **CMAP amplitude** | Low at baseline | Normal | | **SFEMG** | Increased "blocking" and "jitter" | Increased jitter; blocking less prominent | | **Antibodies** | Anti-VGCC (P/Q-type or N-type) | Anti-AChR or anti-MuSK | | **Edrophonium response** | Minimal or absent | Dramatic improvement | **High-Yield:** The **incremental response on RNS is the hallmark electrophysiological finding in LEMS** and is more specific than anti-VGCC antibodies (which can be negative in ~15% of LEMS cases). **Clinical Pearl:** LEMS is often associated with small-cell lung cancer (60% of cases). The combination of proximal weakness, autonomic dysfunction (dry mouth, constipation, erectile dysfunction), and reduced reflexes should raise suspicion for LEMS. **Mnemonic:** **LEMS = Low baseline, Incremental after stimulation** (vs. MG = Normal baseline, Decremental throughout).