THE MALIGNANT NEUROLEPTIC SYNDROME

The neuroleptic malignant syndrome (NMS) was initially described as a life-threatening complication of dopamine receptor antagonist treatmen t. The key features of NMS include extrapyramidal disturbances, hypert hermia and elevation of serum creatin kinase (CK) levels. NMS has also been observed after exposure to other drugs which do not directly blo ck dopaminergic neurotransmission. A syndrome clinically identical wit h NMS is known as the akinetic crisis of Parkinson's disease and can b e triggered by rapid withdrawal of dopaminergic medication in Parkinso nian patients. A common feature of these conditions is the failure of dopaminergic neurotransmission which results in enhanced and unbalance d activity of excitatory amino acid neurotransmitters, such as glutama te. These pathophysiological changes take place in the basal ganglia a nd the hypothalamus. The key step in the management of NMS is to make the correct diagnosis. Outcome is generally good if the causative agen t is withdrawn or Parkinsonian medication restarted. Rehydration and l owering of body temperature are the principal symptomatic measures and are more important than several experimental pharmacological approach es to NMS. These include administration of dopamine receptor agonists such as bromocriptine or lisuride, glutamate receptor antagonists such as amantadine, or antihyperthermia drugs such as dantrolene. Their ro le in the management of NMS is not well defined. Psychotic: patients w ith a history of NMS who need to be retreated with neuroleptic drugs c an be reexposed to classical neuroleptic drugs with careful dosing and inpatient monitoring. Safer and equally effective is probably the tre atment with atypical neuroleptic drugs such as clozapine.