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

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

Bidragets oversatte titel: Niveauer i spinalvæsken af katekolaminer og katekolamin-metabolitter ved Parkinson's sygdom: Effekten af L-DOPA-behandling og forandringer ved L-DOPA-induceret dyskinesi

Andreas Dammann Andersen, Morten Blaabjerg, Michael Binzer, Akram Kamal, Helle Thagesen, Troels Wesenberg Kjær, Egon Stenager, Jan Bert Paul Gramsbergen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

L-DOPA er det mest effektive stof til symptomatisk behandling af Parkinson’s sygdom (PD), men kronisk behandling medfører en maladaptiv proces, som fører til L-DOPA-induceret dyskinesi (LID). Risikofaktorer for LID inkluderer ung alder, alvorligere sværhedsgrad af sygdommen som udgangspunkt og højere dagligt forbrug af L-DOPA. Men biomarkører, som forudser risikoen for at udvikle komplikationer til L-DOPA (såsom bevægeforstyrrelser) findes ikke endnu. Vi har her undersøgt, hvorvidt spinalvæske(CSF)-koncentrationerne af katekolaminer og deres metabolitter er ændrede hos PD-patienter med LID (PD-LID, n=8) sammenligmed med ikke-dyskinetiske PD-patienter, som får L-DOPA-behandling (PD-L, n=6), eller ikke får L-DOPA (PD-N, n=7), såvel som non-PD-kontroller (n=16). Patienterne blev klinisk vurderet vha. Unified Parkinson’s Disease Rating Scale og Unified Dyskinesia Rating Scale, og CSF blev opsamlet efter natlig faste og 1-2 timer efter indtag af L-DOPA eller andre typer anti-PD-medicin. CSF-katekolaminer og deres metabolitter blev analyseret vha. HPLC med elektrokemisk detektion. Vi fandt i) nedsatte niveauer af DOPAC og HVA i PD-patienter, som ikke fik L-DOPA, ii) højere dopamin (DA)-niveauer i PD-LID sammenlignet med kontroller, iii) højere DA/L-DOPA- og lavere DOPAC/DA-ratio’er i PD-LID sammenlignet med PD-L og iv) en aldersrelateret stigning i DA samt nedsat DOPAC/DA-ratio hos kontroller. Disse resultater antyder, at PD-LID har en øget DA-frigivelse fra ikke-dopaminerge celler og en nedsat evne til DA-genoptagelse. Monitorering af DA og DOPAC i CSF fra L-DOPA-behandlede patienter kan måske identificere patienter med risiko for at udvikle LID.
OriginalsprogEngelsk
TidsskriftJournal of Neurochemistry
Vol/bind141
Udgave nummer4
Sider (fra-til)614-625
ISSN0022-3042
DOI
StatusUdgivet - 2017

Fingeraftryk

Cerebrospinal fluid
Dihydroxyphenylalanine
Levodopa
Metabolites
Catecholamines
Parkinson Disease
Cerebrospinal Fluid
Dopamine
Acids
Homovanillic Acid
Disease control
Biomarkers

Emneord

  • Parkinson's sygdom
  • biomarkører
  • dopamin
  • dyskinesi
  • L-DOPA
  • katekolamin
  • HPLC

Citer dette

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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.",
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author = "{Dammann Andersen}, Andreas and Morten Blaabjerg and Michael Binzer and Akram Kamal and Helle Thagesen and Kj{\ae}r, {Troels Wesenberg} and Egon Stenager and Gramsbergen, {Jan Bert Paul}",
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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. / Dammann Andersen, Andreas; Blaabjerg, Morten; Binzer, Michael; Kamal, Akram; Thagesen, Helle ; Kjær, Troels Wesenberg; Stenager, Egon; Gramsbergen, Jan Bert Paul.

I: Journal of Neurochemistry, Bind 141, Nr. 4, 2017, s. 614-625.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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 - Dammann Andersen, Andreas

AU - Blaabjerg, Morten

AU - Binzer, Michael

AU - Kamal, Akram

AU - Thagesen, Helle

AU - Kjær, 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 - Parkinson's sygdom

KW - biomarkører

KW - dopamin

KW - dyskinesi

KW - L-DOPA

KW - katekolamin

KW - HPLC

KW - Parkinson's disease

KW - biomarkers

KW - dopamine

KW - dyskinesia

KW - L-DOPA

KW - catecholamine

KW - HPLC

U2 - 10.1111/jnc.13997

DO - 10.1111/jnc.13997

M3 - Journal article

VL - 141

SP - 614

EP - 625

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 4

ER -