A 55-year-old man with newly diagnosed gastric adenocarcinoma presents with progressive stiffness and rigidity of the trunk and limbs, along with episodic muscle spasms triggered by touch and loud noise. Electromyography shows continuous motor unit activity at rest. Anti-amphiphysin and anti-CRMP5 antibodies are negative, but anti-GABAergic antibodies are positive. What is the most appropriate next step in management?

Question

Accepted Answer

D. Start baclofen and diazepam for symptom control; escalate to immunotherapy (IVIG or plasmapheresis) if no improvement in 2 weeks. ## Clinical Diagnosis
This patient has **Stiff-Person Syndrome (SPS)** — a rare paraneoplastic neurological syndrome associated with gastric and other malignancies.

### Diagnostic Features
| Feature | Finding | Significance |
|---------|---------|---------------|
| Muscle rigidity | Trunk and limbs | Hallmark of SPS |
| Trigger-induced spasms | Touch, noise, emotion | Pathognomonic |
| EMG | Continuous motor unit activity | Confirms diagnosis |
| Anti-GABAergic antibodies | Positive | Diagnostic marker |
| Associated malignancy | Gastric adenocarcinoma | 30% of SPS cases |

**Key Point:** SPS results from autoimmune destruction of GABAergic inhibitory neurons in the spinal cord. Anti-GABAergic antibodies (anti-GABA~A~R, anti-GABA~B~R) are specific markers. The positive antibody test confirms the diagnosis.

## Pathophysiology

```mermaid
flowchart TD
  A[Gastric cancer] --> B[Ectopic antigen expression]
  B --> C[Cross-reactive immune response]
  C --> D[Anti-GABAergic antibodies]
  D --> E[Destruction of spinal GABAergic neurons]
  E --> F[Loss of inhibitory tone]
  F --> G[Unopposed motor neuron firing]
  G --> H[Rigidity and spasms]
```

## Management Strategy

### Step 1: Symptom Control
- **GABA-enhancing agents**: Baclofen (GABA~B~ agonist), benzodiazepines (diazepam, lorazepam)
- Titrate to tolerance; these provide immediate relief

### Step 2: Immunotherapy (if inadequate response)
- **IVIG** (2 g/kg over 3–5 days) — first-line immunotherapy
- **Plasmapheresis** — removes circulating antibodies
- **Corticosteroids** — slower onset (weeks) but useful as adjunct

### Step 3: Cancer Treatment
- Treat underlying gastric cancer (surgery, chemotherapy)
- Tumor control often leads to remission of SPS

**High-Yield:** SPS is NOT uniformly fatal. With combined symptomatic + immunologic + oncologic management, 50–70% of patients achieve significant improvement or remission.

**Clinical Pearl:** Baclofen + diazepam provide rapid symptom relief (days), while IVIG/plasmapheresis address the underlying autoimmunity (weeks). Combining both approaches yields the best outcomes.

Answer

A. Initiate high-dose corticosteroids alone and monitor for response over 4 weeks

Answer

B. Perform immunohistochemistry on the gastric biopsy to confirm GABAergic receptor expression

Answer

C. Refer for palliative care as stiff-person syndrome is uniformly fatal and refractory to treatment

Explanation

Clinical Diagnosis

Diagnostic Features

Pathophysiology

Management Strategy

Step 1: Symptom Control

Step 2: Immunotherapy (if inadequate response)

Step 3: Cancer Treatment

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Feature	Finding	Significance
Muscle rigidity	Trunk and limbs	Hallmark of SPS
Trigger-induced spasms	Touch, noise, emotion	Pathognomonic
EMG	Continuous motor unit activity	Confirms diagnosis
Anti-GABAergic antibodies	Positive	Diagnostic marker
Associated malignancy	Gastric adenocarcinoma	30% of SPS cases