Lambert-Eaton syndrome
Summary
Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder caused by antibodies against presynaptic voltage-gated calcium channels (VGCC) at the neuromuscular junction, leading to decreased acetylcholine release. It causes proximal muscle weakness that improves with repeated activity, and is most commonly associated with small cell lung cancer (paraneoplastic) or other autoimmune conditions.
Detail
Pathophysiology: Autoantibodies target P/Q-type voltage-gated calcium channels on presynaptic nerve terminals at the neuromuscular junction. This impairs calcium influx needed for synaptic vesicle fusion and acetylcholine release, reducing neuromuscular transmission. Unlike myasthenia gravis (postsynaptic nicotinic acetylcholine receptor antibodies), LEMS affects the presynaptic terminal.
Clinical features: Proximal muscle weakness (especially lower limbs), which classically improves with sustained or repeated muscle contraction (due to calcium accumulation overcoming the blockade) - this is called 'facilitation' or incremental response on repetitive nerve stimulation testing, in contrast to the decremental response seen in myasthenia gravis. Patients may also have autonomic symptoms (dry mouth, orthostatic hypotension, erectile dysfunction) and hyporeflexia that improves with exercise. Ptosis and diplopia can occur but are less prominent than in myasthenia gravis.
Associations: Strongly associated with small cell lung carcinoma (paraneoplastic syndrome) - about 50-60% of LEMS cases are paraneoplastic. Can also be associated with other autoimmune diseases without malignancy.
Diagnosis: Electromyography (EMG) with repetitive nerve stimulation shows incremental response (increased amplitude) at high-frequency stimulation, unlike the decremental response in myasthenia gravis. Anti-VGCC antibody testing. Given the strong association with malignancy, screening for small cell lung cancer (CT chest) is essential upon diagnosis.
Treatment: 3,4-diaminopyridine (blocks potassium channels, prolongs depolarization, increases calcium influx and ACh release), immunosuppression (corticosteroids, IVIG, plasmapheresis), and treatment of underlying malignancy if present.
High-yield board points: Remember LEMS = presynaptic, associated with SCLC, improves with exercise/repeated stimulation (unlike MG which worsens with use). Autonomic symptoms are a distinguishing feature from MG.
Sources
- First Aid for the USMLE Step 1
- Kaplan USMLE Step 1 Lecture Notes: Neurology
- Robbins Basic Pathology
- UpToDate: Lambert-Eaton myasthenic syndrome
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