title: Homovanillic acid in CSF of mild stage Parkinson's disease patients correlates with motor impairment.
abstract: In Parkinson's disease (PD), several efforts have been spent in order to find biochemical parameters able to identify the progression of the pathological processes at the basis of the disease. It is already known that advanced PD patients manifesting dyskinesia are featured by the high homovanillic acid (HVA)/dopamine (DA) ratio, suggesting the increased turnover of DA in these patients. Less clear is whether similar changes affect mild and moderate stages of the disease (between 1 and 2.5 of Hoehn & Yahr -H&Y- stage). Hence, here we tested whether cerebrospinal fluid (CSF) concentrations of DA and its major metabolites, either 3,4-dihydroxyphenylacetic acid (DOPAC) or HVA, correlate with motor performance in mild and moderate PD patients. CSF samples were collected after 2 days of anti-PD drugs washout, via lumbar puncture (LP) performed 130 min following administration of oral levodopa (LD) dose (200 mg). LP timing was determined in light of our previous tests clarifying that 2 h after oral LD administration CSF DA concentration reaches a plateau, which was un-respective of PD stage or duration. DA, DOPAC and HVA were assayed by high performance liquid chromatography in a group of 19 patients, distributed in two groups on the basis of the H&Y stage with a cut-off of 1.5. In these PD patients, HVA was correlated with DOPAC (R = 0,56, p < 0,01) and both HVA and DOPAC CSF levels increased in parallel with the motor impairment. More importantly, HVA correlated with motor impairment measured by the Unified Parkinson's Disease Score -III (UPDRS) (R = 0.61; p < 0.0001). The present findings showed the early alteration of the DA pre-synaptic machinery, as documented by the progressive increase of CSF HVA concentrations, which also correlated with PD motor impairment. Therefore, we suggest the potential use of measuring the CSF HVA level as a possible biomarker of PD stage changes in order to monitor the effectiveness of PD-modifying pharmacological therapies.
authors.affiliation: Movement Disorders Centre, Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy. Electronic address: stefani@uniroma2.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Stefani
authors.affiliation: Movement Disorders Centre, Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Pierantozzi
authors.affiliation: Movement Disorders Centre, Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Olivola
authors.affiliation: Neurocenter of Southern Switzerland, Lugano, Switzerland.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Galati
authors.affiliation: Movement Disorders Centre, Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Rocco
authors.initials: R
authors.lastname: Cerroni
authors.affiliation: Movement Disorders Centre, Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Vincenza
authors.initials: V
authors.lastname: D'Angelo
authors.affiliation: Stroke & Dementia Research Centre, St George's University of London, London, United Kingdom.
authors.forename: Atticus H
authors.initials: AH
authors.lastname: Hainsworth
authors.affiliation: Movement Disorders Centre, Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Saviozzi
authors.affiliation: Department of Pharmacy, University of Genoa, Italy.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Fedele
authors.affiliation: Movement Disorders Centre, Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Liguori
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000134:cerebrospinal fluid; D018450:Disease Progression; D005260:Female; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid*; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D019957:Motor Skills Disorders / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000188:drug therapy; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000188:drug therapy
chemical_list: D000978:Antiparkinson Agents; D015415:Biomarkers; D007980:Levodopa; D006719:Homovanillic Acid
keywords: CSF; Dopamine; HVA; Mild Parkinson's disease; Motor impairment