A 38-year-old man with schizophrenia has been on risperidone 6 mg/day for 2 years. He now presents with progressive muscle rigidity, fever (38.5°C), altered mental status, and a serum creatine kinase level of 1200 U/L. Which investigation is most appropriate to confirm the suspected diagnosis?

## Clinical Presentation of Neuroleptic Malignant Syndrome (NMS) The patient presents with the classic tetrad of NMS: muscle rigidity, hyperthermia, altered mental status, and elevated CK. This is a life-threatening complication of antipsychotic use. ### Investigation of Choice: Serum and Urine Myoglobin **Key Point:** Myoglobinuria is the hallmark finding in NMS and indicates rhabdomyolysis—the underlying pathophysiology. Serum myoglobin rises rapidly and is excreted in urine, causing the characteristic dark/cola-colored urine. **High-Yield:** Serum myoglobin is more sensitive than CK for early detection of muscle breakdown and is the gold standard investigation to confirm rhabdomyolysis in NMS. ### Diagnostic Criteria for NMS | Feature | Finding | |---------|----------| | **Temperature** | >38.5°C (often >39°C) | | **Rigidity** | Lead-pipe or cogwheel (uniform) | | **Altered mental status** | Confusion, delirium, coma | | **Autonomic instability** | Tachycardia, hypertension, diaphoresis | | **Laboratory** | ↑↑ CK (>1000), myoglobinuria, ↑ WBC | **Clinical Pearl:** Myoglobin is a low-molecular-weight protein that precipitates in renal tubules at acidic pH, causing acute kidney injury. Detecting myoglobinuria is therefore critical for early intervention (aggressive IV hydration, alkalinization of urine). **Mnemonic: FARM** — **F**ever, **A**ltered mental status, **R**igidity, **M**yoglobinuria (the key lab finding). ### Why This Investigation Matters Confirming myoglobinuria: 1. Establishes rhabdomyolysis as the mechanism 2. Guides urgent fluid resuscitation and urinary alkalinization 3. Predicts risk of acute renal failure 4. Supports discontinuation of the offending antipsychotic [cite:Harrison 21e Ch 385]