Cerebrospinal fluid levels of monoamine metabolites and gamma-aminobutyric acid in neuroleptic malignant syndrome.

To investigate the pathophysiology of neuroleptic malignant syndrome (NMS), we measured various cerebrospinal fluid (CSF) parameters in 11 patients and compared them with 8 age-matched normal controls. Concentrations of homovanillic acid (HVA) were significantly decreased during the active phase of NMS. This finding indicates that the dopaminergic nervous system of the patients was in a state of hypofunction in this phase and supports the central dopamine blockade theory of NMS. Reduced CSF HVA levels were also found after recovery from NMS, suggesting that hypofunction of the dopaminergic system may continue subclinically. The levels of 5-HIAA were decreased in the active phase, but the change was not significant. Therefore, a relationship between the development of NMS and disturbances of serotonin metabolism remains unclear. The levels of noradrenaline and its major metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol increased significantly during the active phase, but returned to normal after recovery. These results show the existence of sympathetic nervous system hyperactivity during the active phase of NMS. The levels of gamma-aminobutyric acid (GABA) were significantly lower in the patients than in the controls. These findings suggest that there is a GABAergic deficiency in NMS. Thus, our study indicates that, in addition to dopamine hypoactivity, disturbances in various neurotransmitter systems are involved in the pathophysiology of NMS.