title: Cerebrospinal fluid levels of catecholamines and its metabolites in Parkinson's disease: effect of l-DOPA treatment and changes in levodopa-induced dyskinesia.
abstract: Levodopa (l-DOPA, l-3,4-dihydroxyphenylalanine) is the most effective drug in the symptomatic treatment of Parkinson's disease (PD), but chronic use initiates a maladaptive process leading to l-DOPA-induced dyskinesia (LID). Risk factors for early onset LID include younger age, more severe disease at baseline and higher daily l-DOPA dose, but biomarkers to predict the risk of motor complications are not yet available. Here, we investigated whether CSF levels of catecholamines and its metabolites are altered in PD patients with LID [PD-LID, n = 8)] as compared to non-dyskinetic PD patients receiving l-DOPA (PD-L, n = 6), or not receiving l-DOPA (PD-N, n = 7) as well as non-PD controls (n = 16). PD patients were clinically assessed using the Unified Parkinson's Disease Rating Scale and Unified Dyskinesia Rating Scale and CSF was collected after overnight fasting and 1-2 h after oral intake of l-DOPA or other anti-Parkinson medication. CSF catecholamines and its metabolites were analyzed by HPLC with electrochemical detection. We observed (i) decreased levels of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid in PD patients not receiving l-DOPA (ii) higher dopamine (DA) levels in PD-LID as compared to controls (iii) higher DA/l-DOPA and lower DOPAC/DA ratio's in PD-LID as compared to PD-L and (iv) an age-dependent increase of DA and decrease of DOPAC/DA ratio in controls. These results suggest increased DA release from non-DA cells and deficient DA re-uptake in PD-LID. Monitoring DA and DOPAC in CSF of l-DOPA-treated PD patients may help identify patients at risk of developing LID.
authors.affiliation: Department of Neurology, Hospital of Southern Jutland, Sønderborg, Denmark.|Institute of Regional Health Research, Center of Southern Jutland, University of Southern Denmark, Aabenraa, Denmark.|Focused Research Group in Neurology, Hospital of Southern Jutland, Aabenraa, Denmark.|Odense Patient data Exploratory Network, Odense University Hospital, Odense, Denmark.
authors.forename: Andreas Dammann
authors.identifier: 0000-0002-9625-1474
authors.initials: AD
authors.lastname: Andersen
authors.affiliation: Department of Neurology, Odense University Hospital, Odense, Denmark.|Department of Neurology, Zealand University Hospital, Roskilde, Denmark.|Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Blaabjerg
authors.affiliation: Institute of Regional Health Research, Center of Southern Jutland, University of Southern Denmark, Aabenraa, Denmark.|Focused Research Group in Neurology, Hospital of Southern Jutland, Aabenraa, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Binzer
authors.affiliation: Department of Neurology, Zealand University Hospital, Roskilde, Denmark.
authors.forename: Akram
authors.initials: A
authors.lastname: Kamal
authors.affiliation: Department of Neurology, Zealand University Hospital, Roskilde, Denmark.
authors.forename: Helle
authors.initials: H
authors.lastname: Thagesen
authors.affiliation: Department of Neurology, Zealand University Hospital, Roskilde, Denmark.
authors.forename: Troels Wesenberg
authors.initials: TW
authors.lastname: Kjaer
authors.affiliation: Department of Neurology, Hospital of Southern Jutland, Sønderborg, Denmark.|Institute of Regional Health Research, Center of Southern Jutland, University of Southern Denmark, Aabenraa, Denmark.|Focused Research Group in Neurology, Hospital of Southern Jutland, Aabenraa, Denmark.|The Multiple Sclerosis Clinic of Southern Jutland, Vejle, Sonderborg, Esbjerg, Denmark.
authors.forename: Egon
authors.initials: E
authors.lastname: Stenager
authors.affiliation: Institute of Molecular Medicine, Neurobiological Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Jan Bert Paul
authors.initials: JBP
authors.lastname: Gramsbergen
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000134:cerebrospinal fluid; D000328:Adult; D000368:Aged; D000375:Aging / Q000134:cerebrospinal fluid; D000978:Antiparkinson Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D002395:Catecholamines / Q000134:cerebrospinal fluid*; D004298:Dopamine / Q000134:cerebrospinal fluid; D004409:Dyskinesia, Drug-Induced / Q000134:cerebrospinal fluid*; D005260:Female; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D007980:Levodopa / Q000009:adverse effects* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000134:cerebrospinal fluid; D010300:Parkinson Disease / Q000134:cerebrospinal fluid*
chemical_list: D000978:Antiparkinson Agents; D002395:Catecholamines; D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid
keywords: 
  HPLC
  ; aging; biomarkers; dopamine; metabolites; neurodegeneration