TY - JOUR

T1 - Cerebrospinal fluid levels of catecholamines and its metabolites in Parkinson's disease

T2 - effect of l-DOPA treatment and changes in levodopa-induced dyskinesia

AU - Andersen, Andreas Dammann

AU - Blaabjerg, Morten

AU - Binzer, Michael

AU - Kamal, Akram

AU - Thagesen, Helle

AU - Kjaer, Troels Wesenberg

AU - Stenager, Egon

AU - Gramsbergen, Jan Bert Paul

N1 - © 2017 International Society for Neurochemistry.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - 3,4-Dihydroxyphenylacetic Acid/cerebrospinal fluid

KW - Adult

KW - Aged

KW - Aging/cerebrospinal fluid

KW - Antiparkinson Agents/adverse effects

KW - Catecholamines/cerebrospinal fluid

KW - Dopamine/cerebrospinal fluid

KW - Dyskinesia, Drug-Induced/cerebrospinal fluid

KW - Female

KW - Homovanillic Acid/cerebrospinal fluid

KW - Humans

KW - Levodopa/adverse effects

KW - Male

KW - Middle Aged

KW - Norepinephrine/cerebrospinal fluid

KW - Parkinson Disease/cerebrospinal fluid

U2 - 10.1111/jnc.13997

DO - 10.1111/jnc.13997

M3 - Journal article

C2 - 28244186

VL - 141

SP - 614

EP - 625

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 4

ER -