Lambert–Eaton syndrome and toxins of the junction
- Lesion
In Lambert-Eaton, antibodies block calcium channels in the nerve ending, often with lung cancer. Toxins like botulinum also stop acetylcholine release.
What it is
Lambert–Eaton myasthenic syndrome is caused by antibodies against presynaptic P/Q-type voltage-gated calcium channels, which reduce calcium entry and acetylcholine release. About half of cases are paraneoplastic, mostly with small cell lung carcinoma, whose cells express the channel. Weakness is proximal, worse in the legs, with autonomic symptoms and reduced reflexes that improve after brief exercise. Congenital myasthenic syndromes are inherited defects of presynaptic, synaptic or postsynaptic proteins. Toxins also act at the junction: botulinum toxin cleaves SNARE proteins and blocks release, organophosphates inhibit acetylcholinesterase, and curare-like agents block the receptor.
Step by step
- In LEMS, tumour cells expressing P/Q calcium channels trigger antibodies that cross-react with nerve terminals.
- Antibodies reduce the number of active calcium channels.
- Less calcium enters with each impulse, so fewer vesicles of acetylcholine are released.
- Repeated firing lets calcium accumulate in the terminal, transiently restoring release (increment).
- Botulinum toxin, by contrast, cleaves SNAREs (SNAP-25, synaptobrevin, syntaxin) and stops vesicle fusion altogether.
Myasthenia gravis vs Lambert–Eaton syndrome
| Feature | Myasthenia gravis | Lambert–Eaton syndrome |
|---|---|---|
| Target | Postsynaptic acetylcholine receptor | Presynaptic P/Q calcium channel |
| Associated tumour | Thymoma | Small cell lung carcinoma |
| Muscles | Eyes and bulbar first | Proximal legs first; eyes rarely |
| Effect of exercise | Weakness worsens | Strength briefly improves |
| Reflexes and autonomic signs | Normal reflexes; no autonomic signs | Reduced reflexes; dry mouth, constipation |
| Repetitive stimulation | Decrement | Increment at high rates |
Clinical notes
- A smoker with proximal leg weakness, dry mouth and absent reflexes that return after exercise: search for small cell lung cancer.
- Botulism is a public health emergency: antitoxin and respiratory support; wound botulism occurs with injection drug use.
- Treating the tumour often improves paraneoplastic LEMS.
Test yourself
Think of the answer, then tap the question to see it.
What is the target of antibodies in Lambert-Eaton syndrome?
Presynaptic P/Q-type voltage-gated calcium channels.
Which tumour is associated with Lambert-Eaton syndrome?
Small cell lung carcinoma.
How does botulinum toxin cause paralysis?
It cleaves SNARE proteins, preventing acetylcholine vesicle release.
How does repetitive stimulation differ between MG and LEMS?
MG shows a decrement; LEMS shows an increment at high-frequency stimulation.
Elsewhere in DurgiPedia
Connections
Microorganisms1
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Small Cell Lung Cancer (StatPearls (NCBI Bookshelf), 2025); Botulism (World Health Organization, 2025); Myasthenia Gravis | MG | MedlinePlus (MedlinePlus, US National Library of Medicine, 2025).
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Representative model, for educational purposes only.