Biochemical alterations during medication withdrawal in Parkinson's disease with and without neuroleptic malignant-like syndrome

The object was to assess alterations in CSF concentrations of monoamine met abolites during withdrawal of medication in patients with Parkinson's disea se in relation to the presence or absence of episodes resembling neurolepti c malignant syndrome (NMS). This syndrome is a fatal condition developing a fter neuroleptic therapy, and a neuroleptic malignant-like syndrome (NMLS) may also occur after withdrawal of antiparkinsonian drugs in patients with Parkinson's disease. Previous biochemical assays showed that the CSF concen tration of the dopamine metabolite homovanillic acid (HVA) is an independen t prognostic factor for development of NMLS in patients with Parkinson's di sease. In the present study, CSF concentrations of HVA, the noradrenaline ( norepinephrine) metabolite 3-methoxy-4-hydroxyphenylethylene glycol, and th e serotonin metabolite 5-hydroxyindole acetic acid were assayed using high performance liquid chromatography with electrochemical detection. The study population consisted of nine patients with Parkinson's disease with NMLS a nd 12 without NMLS, in whom metabolites were assayed during both withdrawal and remedicated periods. Concentrations of HVA in the CSF were significant ly lower during the withdrawal period than the medicated period regardless of whether patients developed NMLS, and HVA concentrations were comparably increased after remedication in both groups. However, HVA concentrations we re significantly lower in patients with NMLS than in those without NMLS dur ing both withdrawal and medicated periods. Other metabolites showed no sign ificant differences. The present data provide further biochemical evidence for extremely suppressed central dopaminergic activity during NMLS, which m ay indicate a narrow safety margin for medication withdrawal in patients wi th Parkinson's disease.