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Levodopa-Induced Dyskinesias in Parkinson Disease Are Independent of the Extent of Striatal Dopaminergic Denervation: A Pharmacological and SPECT Study

Linazasoro, Gurutz MD*; Van Blercom, Nadege MD*; Bergaretxe, Alberto MD†; Fernández Manchola, Iñaki MD‡; Laborda, Enrique MD§; Ruiz Ortega, José Angel MD∥

doi: 10.1097/WNF.0b013e3181b52792
Original Articles

The physiopathology of levodopa-induced dyskinesias (LIDs) is unclear. Presynaptic pharmacokinetic and postsynaptic pharmacodynamic mechanisms may be involved. We have analyzed several clinical and pharmacological parameters, as well as the status of the presynaptic dopamine nigrostriatal pathway by using DaTSCAN, in 14 patients with Parkinson disease who developed early and severe LID despite using low doses of levodopa and 10 patients without this complication despite the use of high levodopa doses. Patients were matched for age at onset, duration, and severity of Parkinson disease. Statistically significant differences were observed only in the duration of LID during the levodopa challenge. However, clear differences were also observed in weight and sex distribution (women with low weight predominate in the group with dyskinesia), severity and duration of LID, and total levodopa dosage. The pattern of response to levodopa and the uptake of (123I)N-w-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane were similar in both groups. These results indicate that the development of LID needs additional contributions beyond nigrostriatal denervation. Factors related to sex and body weight could play an important role. However, these findings should be considered cautiously because of the limited statistical power of the study.

*Centro Investigación Parkinson, Fundación Dr Carlos Elósegi, Policlínica Gipuzkoa, San Sebastián; †Neurology Service, Hospital Bidasoa, Hondarribia; ‡Neurology Service, Hospital Donostia, San Sebastián; §Department of Nuclear Medicine, Instituto Oncológico, San Sebastián; and ∥Departamento de Farmacología, Facultad de Medicina, Universidad del País Vasco, Leioa, Spain.

Address correspondence and reprint requests to Gurutz Linazasoro, Centro Investigación Parkinson, Fundación Dr Carlos Elósegi, Policlínica Guipúzcoa, Parque Tecnológico de Miramón, 174, 20009 San Sebastián, Spain; E-mail: glinazasoro@terra.es

The authors have received a grant from a local institution (Kutxa-Instituto Oncológico) to cover the expenses for the imaging procedures.

The authors have no conflict of interest.

© 2009 Lippincott Williams & Wilkins, Inc.