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Cerebrospinal fluid levels of catecholamines and its metabolites in Parkinson's disease: effect of l ‐ DOPA treatment and changes in levodopa‐induced dyskinesia
Author(s) -
Andersen Andreas Dammann,
Blaabjerg Morten,
Binzer Michael,
Kamal Akram,
Thagesen Helle,
Kjaer Troels Wesenberg,
Stenager Egon,
Gramsbergen Jan Bert Paul
Publication year - 2017
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13997
Subject(s) - homovanillic acid , dyskinesia , parkinson's disease , levodopa , dopamine , cerebrospinal fluid , dihydroxyphenylalanine , medicine , catecholamine , endocrinology , neurotransmitter , gastroenterology , disease , pharmacology , central nervous system , serotonin , receptor
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 .