Cerebrospinal fluid levels of catecholamine metabolites in Parkinson’s disease and L-DOPA-induced dyskinesia

Levodopa (L-DOPA) is effective in the symptomatic treatment of Parkinson’s disease (PD), but chronic use is associated with L-DOPA-induced dyskinesia (LID). In the 6-hydroxydopamine rat model of PD, L-DOPA treatment increases dopamine, its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), as well as 3-O-methyl-DOPA (3-OMD) and tyrosine in the striatum. These changes are most pronounced in dyskinetic rats .(Poster Jesper Christensen, FENS-3253).
Aim:
Investigating whether tyrosine/dopamine and tryptophan/kynurenine metabolites are altered in LID compared to non-dyskinetic PD patients and controls.
Method:
Cerebrospinal fluid (CSF) of 6 age-matched controls and 16 PD patients, (11 receiving levodopa, 6 dyskinetic and 6 not receiving levodopa), was analysed for catecholamines and metabolites by HPLC with electrochemical detection. Samples were collected after overnight fasting and 1 hour after intake of medication.
Results and conclusion:
PD patients receiving levodopa had 10-20 fold higher L-DOPA levels and about 100 fold higher levels of 3-OMD than age-matched controls or PD not receiving L-DOPA. DOPAC levels were not different among controls and subgroups of PD. HVA levels were significantly lower in non-DOPA-treated PD. Ratios of DOPAC/DOPA or HVA/DOPA were much lower in levodopa-treated patients, not distinguishing dyskinetic (N=6) from non-dyskinetic PD patients (N=5). More patients need to be included. Tryptophan/kynurenine metabolites will be analysed using LC coupled to mass spectrometry (MS).