Which paraneoplastic syndrome is most commonly associated with small cell lung cancer and is caused by antibodies against voltage-gated calcium channels?

Question

Accepted Answer

C. Lambert-Eaton myasthenic syndrome. ## 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.

Answer

A. Dermatomyositis

Answer

B. Guillain-Barré syndrome

Answer

D. Myasthenia gravis

Which paraneoplastic syndrome is most commonly associated with small cell lung cancer and is caused by antibodies against voltage-gated calcium channels?

Explanation

Paraneoplastic Syndrome: Lambert-Eaton Myasthenic Syndrome (LEMS)

Pathophysiology

Clinical Features

Diagnostic Findings

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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