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?

Explanation

## 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.