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From the Institute of Neurology, University of Bologna, Italy.
Address correspondence and reprint requests to Dr. Manuela Contin, Institute of Neurology, University of Bologna, Via Foscolo 7, 40123 Bologna, Italy.
Objective: The aims of the study were to follow prospectively the intrasubject progression of idiopathic PD in a cohort of patients using levodopa kinetic-dynamic modeling and to assess the relation between the rate of progression of the disease and patients' different clinical characteristics.
Methods: Thirty-four patients (Hoehn and Yahr stages 1 to 3) enrolled in the longitudinal follow-up. Each patient was examined at 1-year intervals over a median 4 years by a standardized oral levodopa test. The primary measure outcome was the computed half-life of levodopa in the "effect compartment" (t1/2eq), a proposed indicator of nigrostriatal dopaminergic functionality and integrity.
Results: Values of levodopa t1/2eq correlated negatively with severity of symptoms (r = -0.652, p < 0.0001) and decreased over the years together with a worsening of patients' clinical stage (p < 0.0001). The rate of reduction in drug t1/2eq was more rapid in patients at the earlier stages of the disease compared with the more advanced ones, falling from a median annual reduction of 37 minutes in patients at initial Hoehn and Yahr stage 1 to 6.5 minutes in stage 3 patients (p < 0.001). Patients without tremor at onset, otherwise comparable to patients with tremor for baseline values of levodopa t1/2eq, disease severity, duration, and daily dose of levodopa, tended to show a higher rate of reduction in levodopa t1/2eq than patients with tremor. Overall, patients' annual reduction in levodopa t1/2eq over baseline values averaged 17 ± 9%.
Conclusions: These results are in keeping with PET findings on the objective assessment of idiopathic parkinsonism evolution, and they support the suggestion that levodopa pharmacodynamic modeling may offer a practical clinical tool to assess indirectly the functional integrity of the nigrostriatal dopaminergic system over time in parkinsonian patients.
Presented in part at the 12th International Symposium on Parkinson's Disease, London, UK, March 23-26, 1997.
Received February 5, 1998. Accepted in final form May 22, 1998.
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P. Cumming, F. Hermansen, A. Gjedde, M. Contin, R. Riva, P. Martinelli, P. Cortelli, F. Albani, and A. Baruzzi Cerebral dopamine concentrations during levodopa treatment Neurology, October 1, 1999; 53(6): 1374 - 1374. [Full Text]
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O. Suchowersky, S. Reich, J. Perlmutter, T. Zesiewicz, G. Gronseth, and W. J. Weiner Practice Parameter: diagnosis and prognosis of new onset Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology, April 11, 2006; 66(7): 968 - 975. [Abstract] [Full Text] [PDF]
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