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Activity enhances dopaminergic long-duration response in Parkinson disease

2012; Lippincott Williams & Wilkins; Volume: 78; Issue: 15 Linguagem: Inglês

10.1212/wnl.0b013e31824f8056

1526-632X

Un Jung Kang, Peggy Auinger, Stanley Fahn, David Oakes, Ira Shoulson, Karl Kieburtz, Alice Rudolph, Kenneth Marek, John Seibyl, Anthony E. Lang, C. Warren Olanow, Caroline M. Tanner, Giovanni Schifitto, Hongwei Zhao, Lydia Reyes, Aileen Shinaman, Cynthia L. Comella, Christopher G. Goetz, Lucia M. Blasucci, Johan Samanta, Mark Stacy, Kelli Williamson, Mary Harrigan, Paul Greene, Blair Ford, Carol Moskowitz, Daniel Truong, Mayank Pathak, Joseph Jankovic, William G. Ondo, Farah Atassi, Christine Hunter, Carol Jacques, Joseph H. Friedman, Margaret C. Lannon, David Russell, Danna Jennings, B. Fussell, David G. Standaert, Michael A. Schwarzschild, John H. Growdon, Marsha Tennis, Serge Gauthier, Michel Panisset, Jean Hall, Stephen T. Gancher, John P. Hammerstad, Claudia Stone, Barbara Alexander-Brown, Stewart A. Factor, Eric Molho, Diane Brown, Sharon Evans, Jeffrey N. Clark, Bala V. Manyam, Patricia Simpson, Brian Wulbrecht, Jacqueline Whetteckey, W. R. Wayne Martin, Ted E Roberts, Pamela King, Robert A. Hauser, Theresa A. Zesiewicz, Lisa Gauger, Joel M. Trugman, G. Frederick Wooten, Elke Rost‐Ruffner, Joel S. Perlmutter, Brad A. Racette, Oksana Suchowersky, Ranjit Ranawaya, Susan M. Wood, Carol Pantella, Roger Kurlan, Irene Hegeman Richard, N. Shirlene Pearson, John N. Caviness, Charles Adler, Marlene Lind, Tanya Simuni, Andrew Siderowf, Amy Colcher, Mary Lloyd, William J. Weiner, Lisa M. Shulman, William C. Koller, Kelly Lyons, Robert G. Feldman, Marie Saint‐Hilaire, Samuel A. Ellias, Cathi-Ann Thomas, Jorge L. Juncos, Ray L. Watts, Anna Partlow, James W. Tetrud, Daniel M. Togasaki, Tracy Stewart, Margery H. Mark, Jacob I. Sage, Debbie Caputo, Harry J. Gould, Jayaraman Rao, A. D. McKendrick, Mitchell F. Brin, Fabio Danisi, Reina Benabou, Jean Hubble, George W. Paulson, Carson Reider, Alex Birnbaum, Janis M. Miyasaki, Lisa Johnston, Julie So, Rajesh Pahwa, Richard Dubinsky, Zbigniew K. Wszołek, Ryan J. Uitti, Margaret F. Turk, Paul Tuite, David A. Rottenberg, Joy Hansen, Serrano Ramos, Cheryl Waters, Mark Lew, Mickie Welsh, Connie Kawai, Christopher OʼBrien, Rajeev Kumar, Lauren Seeberger, Deborah Judd, Tilak Mendis, Corlane Barclay, David A. Grimes, Laura Sutherland, Ted M. Dawson, Stephen G. Reich, Rebecca A. Dunlop, Roger L. Albin, Kirk A. Frey, K. Wernette,

Botulinum Toxin and Related Neurological Disorders

We tested the hypothesis that dopamine-dependent motor learning mechanism underlies the long-duration response to levodopa in Parkinson disease (PD) based on our studies in a mouse model. By data-mining the motor task performance in dominant and nondominant hands of the subjects in a double-blind randomized trial of levodopa therapy, the effects of activity and dopamine therapy were examined.We data-mined the Earlier versus Later Levodopa Therapy in Parkinson's Disease (ELLDOPA) study published in 2005 and performed statistical analysis comparing the effects of levodopa and dominance of handedness over 42 weeks.The mean change in finger-tapping counts from baseline before the initiation of therapy to predose at 9 weeks and 40 weeks increased more in the dominant compared to nondominant hand in levodopa-treated subjects in a dose-dependent fashion. There was no significant difference in dominant vs nondominant hands in the placebo group. The short-duration response assessed by the difference of postdose performance compared to predose performance at the same visit did not show any significant difference between dominant vs nondominant hands.Active use of the dominant hand and dopamine replacement therapy produces synergistic effect on long-lasting motor task performance during "off" medication state. Such effect was confined to dopamine-responsive symptoms and not seen in dopamine-resistant symptoms such as gait and balance. We propose that long-lasting motor learning facilitated by activity and dopamine is a form of disease modification that is often seen in trials of medications that have symptomatic effects.