Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial
Frances M Weaver, Kenneth Follett, Matthew Stern, Kwan Hur, Crystal Harris, William J Marks Jr, Johannes Rothlind, Oren Sagher, Domenic Reda, Claudia S Moy, Rajesh Pahwa, Kim Burchiel, Penelope Hogarth, Eugene C Lai, John E Duda, Kathryn Holloway, Ali Samii, Stacy Horn, Jeff Bronstein, Gatana Stoner, Jill Heemskerk, Grant D Huang, CSP 468 Study Group, Kenneth Follett, Matthew Stern, Frances Weaver, Dolores Ippolito, Gatana Stoner, Tammy Barnett, Ken Bukowski, Rosemarie DeNicolo, Kwan Hur, Joyce Jimenez, Ping Luo, Jan Motyka, Domenic Reda, Theresa Simon, Bharat Thakkar, Robert Woolson, Carol Fye, William Gagne, Crystal Harris, Julia Buckelew, Carol Fye, Marilyn Garin, Sharon Matzek, Donna Smith, Jill Heemskerk, Claudia Moy, Paul Sheehy, Louis Fiore, Robert Hall, Kevin Stroupe, Kim Burchiel, Kenneth Follett, Carol Fye, Crystal Harris, Jill Heemskerk, Kwan Hur, William Koller, William J Marks Jr, Claudia Moy, Rajesh Pahwa, Domenic Reda, Johannes Rothlind, Oren Sagher, Paul Sheehy, Matthew Stern, Frances Weaver, Roy Bakay, Rick Chappell, Robert Hart, Robert Holloway Jr, George McCabe, Margaret Schenkman, Jamal Taha, Jeff Bronstein, John Duda, Penelope Hogarth, Kathryn Holloway, Stacy Horn, Eugene C Lai, William J Marks Jr, Ali Samii, Farah Atassi, Cecilia Bello, Lisette Bunting-Perry, Tina Conn, Alice Cugley, Nanette Eubank, Linda Fincher, Romay Franks, Tammy Harris, Mariann Haselman, Susan Heath, Miriam Hirsch, Virginia Janovsky, Elaine Lanier, Mary Lloyd, Susan Loehner, Susan O'Connor, Ligaya Ordonez, Heather Maccarone, Kelli Massey-Makhoul, Mary Matthews, Elizabeth Meyn, Keiko Mimura, Wes Morrow, Tammy Searles, Jamye Valotta, Usha Vasthare, Monica Volz, Constance Ward, Rebecca Warker, Heidi Watson, Pamela Willson, Mark Baron, Matthew Brodsky, Jeff Bronstein, Vincent Calabrese, Gordon Campbell, Amy Colcher, John Duda, Emad Faraq, Eva Henry, Penelope Hogarth, Jyh-Gong Hou, Gail Kang, Galit Kleiner-Fisman, Jeff Kraakevik, Stacy Horn, Eugene C Lai, William J Marks Jr, John Nutt, Jill Ostrem, Ali Samii, Aliya Sarwar, Indu Subramanian, Zeba Vanek, Gordon Baltuch, Kim Burchiel, Antonio DeSalles, Jorge Eller, Kathryn Holloway, Paul Larson, Richard Simpson, Philip Starr, William Carne, Tom Erikson, Jurg Jaggi, Jeffrey Kreutzer, Mario Mendez, Paul Moberg, John Ragland, Johannes Rothlind, Ronald Seel, Elizabeth Soety, Daniel Storzbach, Alexander Troster, Michele York, Frances M Weaver, Kenneth Follett, Matthew Stern, Kwan Hur, Crystal Harris, William J Marks Jr, Johannes Rothlind, Oren Sagher, Domenic Reda, Claudia S Moy, Rajesh Pahwa, Kim Burchiel, Penelope Hogarth, Eugene C Lai, John E Duda, Kathryn Holloway, Ali Samii, Stacy Horn, Jeff Bronstein, Gatana Stoner, Jill Heemskerk, Grant D Huang, CSP 468 Study Group, Kenneth Follett, Matthew Stern, Frances Weaver, Dolores Ippolito, Gatana Stoner, Tammy Barnett, Ken Bukowski, Rosemarie DeNicolo, Kwan Hur, Joyce Jimenez, Ping Luo, Jan Motyka, Domenic Reda, Theresa Simon, Bharat Thakkar, Robert Woolson, Carol Fye, William Gagne, Crystal Harris, Julia Buckelew, Carol Fye, Marilyn Garin, Sharon Matzek, Donna Smith, Jill Heemskerk, Claudia Moy, Paul Sheehy, Louis Fiore, Robert Hall, Kevin Stroupe, Kim Burchiel, Kenneth Follett, Carol Fye, Crystal Harris, Jill Heemskerk, Kwan Hur, William Koller, William J Marks Jr, Claudia Moy, Rajesh Pahwa, Domenic Reda, Johannes Rothlind, Oren Sagher, Paul Sheehy, Matthew Stern, Frances Weaver, Roy Bakay, Rick Chappell, Robert Hart, Robert Holloway Jr, George McCabe, Margaret Schenkman, Jamal Taha, Jeff Bronstein, John Duda, Penelope Hogarth, Kathryn Holloway, Stacy Horn, Eugene C Lai, William J Marks Jr, Ali Samii, Farah Atassi, Cecilia Bello, Lisette Bunting-Perry, Tina Conn, Alice Cugley, Nanette Eubank, Linda Fincher, Romay Franks, Tammy Harris, Mariann Haselman, Susan Heath, Miriam Hirsch, Virginia Janovsky, Elaine Lanier, Mary Lloyd, Susan Loehner, Susan O'Connor, Ligaya Ordonez, Heather Maccarone, Kelli Massey-Makhoul, Mary Matthews, Elizabeth Meyn, Keiko Mimura, Wes Morrow, Tammy Searles, Jamye Valotta, Usha Vasthare, Monica Volz, Constance Ward, Rebecca Warker, Heidi Watson, Pamela Willson, Mark Baron, Matthew Brodsky, Jeff Bronstein, Vincent Calabrese, Gordon Campbell, Amy Colcher, John Duda, Emad Faraq, Eva Henry, Penelope Hogarth, Jyh-Gong Hou, Gail Kang, Galit Kleiner-Fisman, Jeff Kraakevik, Stacy Horn, Eugene C Lai, William J Marks Jr, John Nutt, Jill Ostrem, Ali Samii, Aliya Sarwar, Indu Subramanian, Zeba Vanek, Gordon Baltuch, Kim Burchiel, Antonio DeSalles, Jorge Eller, Kathryn Holloway, Paul Larson, Richard Simpson, Philip Starr, William Carne, Tom Erikson, Jurg Jaggi, Jeffrey Kreutzer, Mario Mendez, Paul Moberg, John Ragland, Johannes Rothlind, Ronald Seel, Elizabeth Soety, Daniel Storzbach, Alexander Troster, Michele York
Abstract
Context: Deep brain stimulation is an accepted treatment for advanced Parkinson disease (PD), although there are few randomized trials comparing treatments, and most studies exclude older patients.
Objective: To compare 6-month outcomes for patients with PD who received deep brain stimulation or best medical therapy.
Design, setting, and patients: Randomized controlled trial of patients who received either deep brain stimulation or best medical therapy, stratified by study site and patient age (< 70 years vs > or = 70 years) at 7 Veterans Affairs and 6 university hospitals between May 2002 and October 2005. A total of 255 patients with PD (Hoehn and Yahr stage > or = 2 while not taking medications) were enrolled; 25% were aged 70 years or older. The final 6-month follow-up visit occurred in May 2006.
Intervention: Bilateral deep brain stimulation of the subthalamic nucleus (n = 60) or globus pallidus (n = 61). Patients receiving best medical therapy (n = 134) were actively managed by movement disorder neurologists.
Main outcome measures: The primary outcome was time spent in the "on" state (good motor control with unimpeded motor function) without troubling dyskinesia, using motor diaries. Other outcomes included motor function, quality of life, neurocognitive function, and adverse events.
Results: Patients who received deep brain stimulation gained a mean of 4.6 h/d of on time without troubling dyskinesia compared with 0 h/d for patients who received best medical therapy (between group mean difference, 4.5 h/d [95% CI, 3.7-5.4 h/d]; P < .001). Motor function improved significantly (P < .001) with deep brain stimulation vs best medical therapy, such that 71% of deep brain stimulation patients and 32% of best medical therapy patients experienced clinically meaningful motor function improvements (> or = 5 points). Compared with the best medical therapy group, the deep brain stimulation group experienced significant improvements in the summary measure of quality of life and on 7 of 8 PD quality-of-life scores (P < .001). Neurocognitive testing revealed small decrements in some areas of information processing for patients receiving deep brain stimulation vs best medical therapy. At least 1 serious adverse event occurred in 49 deep brain stimulation patients and 15 best medical therapy patients (P < .001), including 39 adverse events related to the surgical procedure and 1 death secondary to cerebral hemorrhage.
Conclusion: In this randomized controlled trial of patients with advanced PD, deep brain stimulation was more effective than best medical therapy in improving on time without troubling dyskinesias, motor function, and quality of life at 6 months, but was associated with an increased risk of serious adverse events.
Trial registration: clinicaltrials.gov Identifier: NCT00056563.
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Source: PubMed