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Clinical correlates of levodopa-induced dopamine release in Parkinson disease

A PET study

From the MRC Clinical Sciences Centre and Division of Neurosciences (N.P., Y.F.T., G.H., D.J.B., P.P.), Faculty of Medicine, Imperial College, Hammersmith Hospital, and Reta Lila Weston Institute of Neurological Studies and the National Hospital for Neurology and Neurosurgery (A.H.E., A.J.L.), London, UK.

Address correspondence and reprint requests to Dr. P. Piccini, MRC Clinical Sciences Centre and Division of Neurosciences, Faculty of Medicine, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK; e-mail: paola.piccini{at}csc.mrc.ac.uk

Objective: To evaluate the relationship between clinical improvement and in vivo synaptic dopamine (DA) release after a single oral dose of levodopa (LD) in patients with advanced Parkinson disease (PD).

Methods: We studied 16 patients with advanced PD with [¹¹C]raclopride (RAC) PET. Each patient had RAC PET twice: once when medication had been withdrawn and once after an LD challenge. On the day of the LD challenge scan, oral 250 mg LD/25 mg carbidopa was given before scanning. Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were rated in an "off" state before LD and again at the end of PET.

Results: All the patients were still in "on" state at the end of their LD challenge RAC PET scans. Following LD, mean caudate and putamen RAC binding potentials (BPs) were significantly lower vs baseline, consistent with increased synaptic DA. Individual LD-induced improvements in UPDRS score correlated significantly with reductions in putaminal BP. Additionally, large putaminal RAC BP changes were associated with higher dyskinesia scores. When motor UPDRS subitems were examined, improvements in rigidity and bradykinesia, but not in tremor or axial symptoms, correlated with putamen DA release.

Conclusion: In advanced Parkinson disease, the improvement of rigidity and bradykinesia and the presence of dyskinesias after a single dose of oral levodopa are governed by the level of dopamine generated at striatal D2 receptors. In contrast, relief of parkinsonian tremor and axial symptoms is not related to striatal synaptic dopamine levels and presumably occurs via extrastriatal mechanisms.

Disclosure: The authors report no conflicts of interest.

Received February 28, 2006. Accepted in final form June 27, 2006.

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