Dissociation of Metabolic and Neurovascular Responses to Levodopa in the Treatment of Parkinson's Disease

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Abstract
We compared the metabolic and neurovascular effects of levodopa (LD) therapy for Parkinson9s disease (PD). Eleven PD patients were scanned with both [15O]-H2O and [18F]-fluorodeoxyglucose positron emission tomography in the unmedicated state and during intravenous LD infusion. Images were used to quantify LD-mediated changes in the expression of motor- and cognition-related PD covariance patterns in scans of cerebral blood flow (CBF) and cerebral metabolic rate for glucose (CMR). These changes in network activity were compared with those occurring during subthalamic nucleus (STN) deep brain stimulation (DBS), and those observed in a test–retest PD control group. Separate voxel-based searches were conducted to identify individual regions with dissociated treatment-mediated changes in local cerebral blood flow and metabolism. We found a significant dissociation between CBF and CMR in the modulation of the PD motor-related network by LD treatment (p < 0.001). This dissociation was characterized by reductions in network activity in the CMR scans (p < 0.003) occurring concurrently with increases in the CBF scans (p < 0.01). Flow–metabolism dissociation was also evident at the regional level, with LD-mediated reductions in CMR and increases in CBF in the putamen/globus pallidus, dorsal midbrain/pons, STN, and ventral thalamus. CBF responses to LD in the putamen and pons were relatively greater in patients exhibiting drug-induced dyskinesia. In contrast, flow–metabolism dissociation was not present in the STN DBS treatment group or in the PD control group. These findings suggest that flow–metabolism dissociation is a distinctive feature of LD treatment. This phenomenon may be especially pronounced in patients with LD-induced dyskinesia.