Clinical presentation of neuroleptic malignant syndrome

Although neuroleptic malignant syndrome can occur any time during treatment with antipsychotic drugs, it usually occurs within 1 to 2 weeks of starting treatment or increasing the dose.

Neuroleptic malignant syndrome develops over days. This is an important distinguishing feature from serotonergic toxidrome, which has a more rapid onset and a wide spectrum of clinical severity.

The classic tetrad of clinical features in neuroleptic malignant syndrome is:

• extrapyramidal effects—‘lead-pipe’ rigidity, bradykinesia or akinesia, dystonia, abnormal movement and posture, dysphagia, tremor
• temperature dysregulation, including hyperthermia with a temperature of more than 39ºC
• autonomic effects—tachycardia, hypertension, labile blood pressure, sweating, tachypnoea
• central nervous system effects—drowsiness, confusion, coma, mutism, incontinence.

Abnormal investigation findings common (though not specific) in neuroleptic malignant syndrome include:

• serum creatine kinase concentration more than 3 times the upper limit of normal
• leucocytosis
• low serum iron concentration
• diffuse slowing on an electroencephalogram, consistent with a metabolic encephalopathy
• cerebrospinal fluid examination (lumbar puncture) may be normal, or have a slightly raised protein concentration.

Computed tomography and magnetic resonance imaging of the brain are normal in neuroleptic malignant syndrome.