A 58-year-old male smoker presents with progressive proximal muscle weakness and autonomic dysfunction. Electromyography shows facilitation with high-frequency stimulation. Which is the most common malignancy associated with this paraneoplastic syndrome?

Question

Accepted Answer

C. Small cell lung cancer. ## Lambert-Eaton Myasthenic Syndrome (LEMS)

### Clinical Presentation
The patient presents with the classic triad of LEMS:
- Proximal muscle weakness (lower limbs > upper limbs)
- Autonomic dysfunction (dry mouth, impotence, constipation)
- Areflexia or hyporeflexia

### Electrophysiology
**Key Point:** Facilitation with high-frequency stimulation (>10 Hz) is pathognomonic for LEMS. This distinguishes it from myasthenia gravis, which shows decremental response.

### Paraneoplastic Association

| Malignancy | Frequency | Mechanism |
|---|---|---|
| Small cell lung cancer (SCLC) | 50–60% | Anti-VGCC (P/Q-type) antibodies |
| Gastric cancer | 5–10% | Anti-VGCC antibodies |
| Lymphoma | 3–5% | Anti-VGCC antibodies |
| Other lung cancers | <5% | Rare |

**High-Yield:** SCLC accounts for >50% of LEMS cases. In a smoker with LEMS, SCLC must be excluded with imaging (chest X-ray, CT).

### Pathophysiology
LEMS is caused by autoantibodies against **voltage-gated calcium channels (VGCC)** at the presynaptic terminal. This reduces acetylcholine release, leading to muscle weakness.

**Clinical Pearl:** Unlike myasthenia gravis (which worsens with fatigue), LEMS improves with exercise—a key diagnostic clue.

### Management
1. Screen for occult malignancy (especially SCLC)
2. Immunotherapy (IVIg, plasmapheresis)
3. Symptomatic: 3,4-diaminopyridine (K^+^ channel blocker)
4. Treat underlying cancer

**Mnemonic:** LEMS = **L**ow acetylcholine release, **E**nhanced by exercise, **M**alignancy (SCLC), **S**eropositive for VGCC antibodies.

Answer

A. Gastric adenocarcinoma

Answer

B. Pancreatic cancer

Answer

D. Renal cell carcinoma

A 58-year-old male smoker presents with progressive proximal muscle weakness and autonomic dysfunction. Electromyography shows facilitation with high-frequency stimulation. Which is the most common malignancy associated with this paraneoplastic syndrome?

Explanation

Lambert-Eaton Myasthenic Syndrome (LEMS)

Clinical Presentation

Electrophysiology

Paraneoplastic Association

Pathophysiology

Management

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Malignancy	Frequency	Mechanism
Small cell lung cancer (SCLC)	50–60%	Anti-VGCC (P/Q-type) antibodies
Gastric cancer	5–10%	Anti-VGCC antibodies
Lymphoma	3–5%	Anti-VGCC antibodies
Other lung cancers	<5%	Rare