Neuroleptic Malignant Syndrome - Signs and Symptoms

Signs and Symptoms

The first symptoms of neuroleptic malignant syndrome are usually muscle cramps and tremors, fever, symptoms of autonomic nervous system instability such as unstable blood pressure, and alterations in mental status (agitation, delirium, or coma). Once symptoms appear, they may progress rapidly and reach peak intensity in as little as three days. These symptoms can last anywhere from eight hours to forty days. The muscular symptoms are most likely caused by blockade of the dopamine receptor D₂, leading to abnormal function of the basal ganglia similar to that seen in Parkinson's disease.

A raised white blood cell count and creatine phosphokinase (CPK) plasma concentration will be reported due to increased muscular activity and rhabdomyolysis (destruction of muscle tissue). The patient may suffer hypertensive crisis and metabolic acidosis. A non-generalized slowing on an EEG is reported in around 50% of cases.

The fever is believed to be caused by hypothalamic dopamine receptor blockade. The peripheral problems (the white blood cell and CPK count) are caused by the antipsychotic drugs. They cause an increased calcium release from the sarcoplasmic reticulum of muscle cells which can result in rigidity and eventual cell breakdown. No major studies have reported an explanation for the abnormal EEG, but it is likely also attributable to dopamine blockage leading to changes in neuronal pathways.

Unfortunately, symptoms are sometimes misinterpreted by doctors as symptoms of mental illness, delaying treatment. NMS is less likely if a person has previously been stable for a period of time on antipsychotics, especially in situations where the dose has not been changed and there are no issues of noncompliance or consumption of psychoactive substances known to worsen psychosis.