## Paraneoplastic Syndrome: Lambert-Eaton Myasthenic Syndrome (LEMS) **Key Point:** LEMS is a paraneoplastic syndrome caused by autoantibodies against voltage-gated calcium channels (VGCC) at the presynaptic terminal of the neuromuscular junction. **High-Yield:** Small cell lung cancer (SCLC) is the malignancy most frequently associated with LEMS, occurring in 50–60% of LEMS patients. The remaining cases are idiopathic or associated with other malignancies (gastric, breast, lymphoma). ### Pathophysiology Autoantibodies bind to VGCC → reduced calcium influx → decreased acetylcholine release → muscle weakness. ### Clinical Features - **Proximal muscle weakness** (legs > arms) - **Autonomic symptoms:** dry mouth, impotence, constipation - **Diminished or absent deep tendon reflexes** (unlike myasthenia gravis) - **Facilitation phenomenon:** brief high-frequency muscle stimulation temporarily improves strength ### Diagnostic Findings | Feature | LEMS | Myasthenia Gravis | | --- | --- | --- | | **Antibody target** | VGCC | Acetylcholine receptor (AChR) | | **Associated malignancy** | SCLC (50–60%) | Thymoma (10–15%) | | **Reflexes** | Diminished/absent | Normal | | **Facilitation** | Present (characteristic) | Absent | | **Repetitive nerve stimulation** | Incremental response | Decremental response | **Clinical Pearl:** The presence of LEMS should prompt aggressive screening for SCLC, even in asymptomatic patients, as malignancy may precede neurological symptoms by months to years. **Mnemonic:** LEMS = **L**ow **E**nergy **M**uscle **S**trength (proximal weakness, fatigue) + **L**ung cancer association.
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