Metabolic correlates of levodopa response in Parkinson's disease

Objective: To assess the effects of levodopa on resting-state brain metabol ism in PD. Background: In previous studies the authors used [F-18] fluorode oxyglucose (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 levod opa infusion to quantify the effects of dopamine replacement on regional me tabolism and PDRP network activity. They tested the hypothesis that clinica l 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 Ya hr stage, 1.9 +/- 0.7, mean +/- SD); subjects were scanned both off levodop a and during an individually titrated constant-rate IV levodopa infusion. T he authors used statistical parametric mapping to identify significant chan ges in regional brain metabolism that occurred with this intervention. They also quantified levodopa-induced changes in PDRP expression. Metabolic cha nges with levodopa correlated with clinical improvement as measured by chan ges in Unified PD Rating Scale (UPDRS) motor scores. Results: Levodopa infu sion improved UPDRS motor ratings (30.6% +/- 12.0%, p < 0.002) and signific antly decreased regional glucose metabolism in the left putamen, right thal amus, bilateral cerebellum, and left primary motor cortex (p < 0.001). Chan ges in pallidal metabolism correlated significantly with clinical improveme nt 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 acti vity mediated by levodopa correlated significantly with clinical improvemen t in UPDRS motor ratings (r = -0.78, p < 0.04). Conclusion: Levodopa reduce s brain metabolism in the putamen, thalamus, and cerebellum in patients wit h PD. Additionally, levodopa reduces PD-related pattern activity, and the d egree of network suppression correlates with clinical improvement. The resp onse to dopaminergic therapy in Patients with PD may be determined by the m odulation of cortico-striato-pallido-thalamocortical pathways.