Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial.
BACKGROUND
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.


METHODS
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.


METHODS
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.


METHODS
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.


CONCLUSIONS
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.


BACKGROUND
clinicaltrials.gov Identifier: NCT00056563.
Weaver
Frances M
FM
Hines VA Hospital, Center for Management of Complex Chronic Care, Hines, Illinois 60141, USA. Frances.Weaver@va.gov
Follett
Kenneth
K
Stern
Matthew
M
Hur
Kwan
K
Harris
Crystal
C
Marks
William J
WJ
Rothlind
Johannes
J
Sagher
Oren
O
Reda
Domenic
D
Moy
Claudia S
CS
Pahwa
Rajesh
R
Burchiel
Kim
K
Hogarth
Penelope
P
Lai
Eugene C
EC
Duda
John E
JE
Holloway
Kathryn
K
Samii
Ali
A
Horn
Stacy
S
Bronstein
Jeff
J
Stoner
Gatana
G
Heemskerk
Jill
J
Huang
Grant D
GD
D000368:Aged; D003071:Cognition; D046690:Deep Brain Stimulation / Q000009:adverse effects; D005260:Female; D005917:Globus Pallidus; D006801:Humans; D008297:Male; D008875:Middle Aged; D009048:Motor Skills; D010300:Parkinson Disease / Q000628:therapy*; D011788:Quality of Life; D020531:Subthalamic Nucleus