Metabolic correlates of levodopa response in Parkinson's disease.
OBJECTIVE
To assess the effects of levodopa on resting-state brain metabolism in PD.


BACKGROUND
In previous studies the authors used [18F] fluorodeoxyglucose (FDG) and PET to quantify regional metabolic abnormalities in PD. They found that this disease is characterized reproducibly by a specific abnormal PD-related pattern (PDRP). In this study the authors used IV levodopa infusion to quantify the effects of dopamine replacement on regional metabolism and PDRP network activity. They tested the hypothesis that clinical response to dopaminergic therapy correlates with these metabolic changes.


METHODS
The authors used FDG/PET to measure resting-state regional brain metabolism in seven patients with PD (age, 59.4 +/- 4.2 years; Hoehn and Yahr stage, 1.9 +/- 0.7, mean +/- SD); subjects were scanned both off levodopa and during an individually titrated constant-rate IV levodopa infusion. The authors used statistical parametric mapping to identify significant changes in regional brain metabolism that occurred with this intervention. They also quantified levodopa-induced changes in PDRP expression. Metabolic changes with levodopa correlated with clinical improvement as measured by changes in Unified PD Rating Scale (UPDRS) motor scores.


RESULTS
Levodopa infusion improved UPDRS motor ratings (30.6% +/- 12.0%, p < 0.002) and significantly decreased regional glucose metabolism in the left putamen, right thalamus, bilateral cerebellum, and left primary motor cortex (p < 0.001). Changes in pallidal metabolism correlated significantly with clinical improvement in UPDRS motor ratings (p < 0.01). Levodopa infusion also resulted in a significant (p = 0.01) decline in PDRP expression. The changes in PDRP activity mediated by levodopa correlated significantly with clinical improvement in UPDRS motor ratings (r = -0.78, p < 0.04).


CONCLUSIONS
Levodopa reduces brain metabolism in the putamen, thalamus, and cerebellum in patients with PD. Additionally, levodopa reduces PD-related pattern activity, and the degree of network suppression correlates with clinical improvement. The response to dopaminergic therapy in Patients with PD may be determined by the modulation of cortico-striato-pallido-thalamocortical pathways.
Feigin
A
A
Center for Neuroscience Research, North Shore University Hospital, Manhasset, NY 11030, USA. asfeigin@aol.com
Fukuda
M
M
Dhawan
V
V
Przedborski
S
S
Jackson-Lewis
V
V
Mentis
M J
MJ
Moeller
J R
JR
Eidelberg
D
D
D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects; D001931:Brain Mapping; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007980:Levodopa / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination / Q000187:drug effects; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000188:drug therapy*; D012016:Reference Values; D014055:Tomography, Emission-Computed
D001786:Blood Glucose; D019788:Fluorodeoxyglucose F18; D007980:Levodopa