Cerebrospinal Fluid Of Parkinson's Disease Patients Research Articles

Homovanillic acid in the cerebrospinal fluid of Parkinsonian patients.

SUMMARY:Determinations of CSF HVA before and after Probenecid administration were made in 41 patients with Parkinson’s disease. The means of HVA concentration were lower than those of controls but no correlation with clinical data was found. A negative correlation was demonstrated between post-probenecid HVA levels and subsequent score improvement with L-DOPA at 3,6 and 12 months. Post-probenecid HVA levels suggest that there are distinct forms of parkinsonism and could predict the response to L-DOPA therapy.

Highly sensitive assay for dopamine-beta-hydroxylase activity in human cerebrospinal fluid by high performance liquid chromatography-electrochemical detection: properties of the enzyme.

This paper describes a new, sensitive assay for dopamine-beta-hydroxylase (DBH) activity in human cerebrospinal fluid (CSF), serum and brain tissues by high performance liquid chromatography (HPLC) with electrochemical detection (ED). Dopamine (DA) was used as a substrate and was incubated under optimal conditions. Norepinephrine (NE) formed enzymatically from DA was isolated by a double-column procedure, the first column of Dowex-50-H+ and the second column of aluminum oxide. NE was adsorbed on the second aluminum oxide column and then eluted with 0.5 M-hydrochloric acid and assayed by HPLC-ED. Epinephrine (EN) was added to each incubation mixture as an internal standard, and this assay was therefore highly reproducible. The peak height in HPLC was linear from 500 fmol to 100 pmol of NE and EN. The lower limit of detection for NE formed enzymatically was about 30 pmol, which indicated that the sensitivity of this procedure was comparable to that of radioassay procedures. We applied the method to measurement of the activity of and examination of some of the characteristics of DBH in human CSF. DBH activity in CSF of Parkinsonian patients was lower than that of control patients. The properties of DBH in human CSF were similar to those in serum and adrenal medulla.

Acid monoamine metabolites in the cerebrospinal fluid of Parkinsonian patients treated with levodopa alone or combined with a decarboxylase inhibitor.

Concentrations of homovanijlic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) were studied before and during treatment of 151 parkinsonian patients with levodopa alone or combined with a decarboxylase inhibitor. A particular attempt was made in this study to determine whether any correlation exists between the concentrations of these acid monoamine metabolites in the CSF before and during treatment as well as after administration of probenecid and the therapeutic response and side-effects of the treatment. In patients with Parkinson’s disease the concentrations of HVA and 5-HIAA in the CSF before therapy and after administration of probenecid were found to be significantly lower than those in control subjects. Statistical analyses showed that these variables could not be used to predict the clinical response to treatment. Long-term treatment with levodopa alone or combined with a decarboxylase inhibitor induced an increase in the concentration of HVA in the CSF which correlated significantly with the dose of the drug but not with the clinical improvement. However, the concentrations of HVA during combined treatment were considerably lower than during treatment with levodopa alone, using therapeutically equivalent dosages. Obviously, a part of the HVA found in the CSF during levodopa treatment originates from the brain capillary walls. Treatment with levodopa and decarboxylase inhibitor decreased the concentration of 5-HIAA in the CSF. During treatment with levodopa alone, there was a significant negative correlation with the dose of levodopa as well as with libido and psychotic behavior after 6 and 12 months’ treatment, respectively.

Phenolic acid concentrations in the lumbar cerebrospinal fluid of Parkinsonian patients treated with L-dopa.

The acid metabolites of dopamine and 5-hydroxytryptamine were estimated in the lumbar cerebrospinal fluid (CSF) of Parkinsonian patients both before and during treatment with l-dopa, the amino acid precursor of dopamine. An attempt was made to relate clinical improvement to the biochemical results. The dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, showed increases related to the dose of l-dopa, the increase in homovanillic acid concentration being proportionately greater than that of 3,4-dihydroxyphenylacetic acid. The concentration of the 5-hydroxytryptamine metabolite, 5-hydroxyindol-3ylacetic acid, was unaltered by the drug. Clinical improvement, which in the early stages was evident particularly in the bradykinesia, was found to occur at doses of l-dopa greater than 1·5 g/day. Effective doses of l-dopa gave rise to concentrations of dopamine metabolites in the CSF which were greater than normal. Possible implications of these findings are discussed.