Neuroleptic Malignant Syndrome
A 28-year-old man with schizophrenia had his haloperidol dose doubled five days ago. He is now confused, with temperature 40.1 °C, pulse 126 beats/min and blood pressure 160/95 mm Hg. There is generalised lead-pipe rigidity without clonus or hyperreflexia. Creatine kinase is 6800 U/L, white cell count 15 × 10⁹/L, and the urine is dark. What is the most likely diagnosis?
- A.Acute dystonic reaction
- B.Serotonin syndrome
- C.Neuroleptic malignant syndromeCorrect
- D.Anticholinergic toxidrome
Explanation
Neuroleptic malignant syndrome is an idiosyncratic reaction to dopamine D2 receptor blockade, most often after starting or escalating a high-potency typical antipsychotic such as haloperidol, and it can also follow abrupt withdrawal of dopaminergic therapy in Parkinson disease. Loss of dopaminergic tone in the hypothalamus impairs thermoregulation while nigrostriatal blockade produces severe muscular rigidity, and sustained contraction generates heat and rhabdomyolysis. The tetrad is hyperthermia, generalised lead-pipe rigidity, altered mental status and autonomic instability, with markedly elevated creatine kinase, leucocytosis, and myoglobinuria that causes dark urine and acute kidney injury. Onset is typically over one to three days and the syndrome evolves more slowly than serotonin syndrome. Treatment is immediate withdrawal of the offending drug, aggressive cooling, intravenous fluids to protect the kidneys, and benzodiazepines, with dantrolene or bromocriptine in severe cases. Serotonin syndrome is distinguished by rapid onset within hours of a serotonergic drug, and by lower limb predominant clonus, hyperreflexia, mydriasis, agitation and diarrhoea rather than lead-pipe rigidity. Acute dystonia causes torticollis or oculogyric crisis without fever and responds within minutes to intramuscular benztropine or diphenhydramine. Anticholinergic toxicity gives dry flushed skin, urinary retention and delirium without rigidity or creatine kinase rise.
Why each option
- A.
- Acute dystonia produces torticollis or oculogyric crisis without fever or rhabdomyolysis and reverses rapidly with anticholinergics.
- B.
- Serotonin syndrome begins within hours of a serotonergic agent and features clonus, hyperreflexia and diarrhoea rather than lead-pipe rigidity.
- C.
- Correct. Hyperthermia, lead-pipe rigidity, altered mental status, autonomic instability and a very high creatine kinase after a haloperidol increase define this syndrome.
- D.
- Anticholinergic toxicity causes dry flushed skin, mydriasis, retention and delirium, but not rigidity or creatine kinase elevation.
Reference: DSM-5-TR, 2022; UpToDate 2025, Neuroleptic malignant syndrome
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