Loss of long-duration response to levodopa over time in PD - Implications for wearing-off

Objective: To determine the modifications of the long-duration response to levodopa in PD over a 1-year period. Background: The development of predict able motor fluctuations in PD has been attributed mainly to modifications o ver time of the short-duration response to levodopa, whereas the role of th e long-duration response has not been widely investigated. Methods: In 17 p atients with PD the authors examined prospectively both the short-duration response and the long-duration response to levodopa under standardized cond itions on two different occasions separated by a period of approximately 1 year (11.7 +/- 3.6 months). Results: At the end of the follow-up period, th e short-duration response increased in magnitude but did not change signifi cantly in duration. A total of 24% of patients lost the long-duration respo nse 1 year after their first examination, but a sustained long-duration res ponse could be reestablished by shortening the interdose interval for levod opa intake. Moreover, the duration of the long-duration response after disc ontinuation of treatment became significantly shorter during 1 year. Conclu sion: Modifications of the long-duration response may have a pivotal role i n generating a fluctuating response, and suggest that therapeutic strategie s based on maintenance of the long-duration response should be sought to av oid the appearance of motor fluctuations.