Subthalamic nucleus deep brain stimulation in early stage Parkinson's disease.
BACKGROUND
Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson's disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD.


METHODS
Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50-75, on medication ≥6 months but ≤4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n = 15) or DBS + ODT (n = 15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months.


RESULTS
As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. Medication requirements in the DBS + ODT group were lower at all time points with a maximal difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS + ODT group suffered serious adverse events; remaining adverse events were mild or transient.


CONCLUSIONS
This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD.
Department of Neurology, Vanderbilt University Medical Center, USA. Electronic address: david.charles@vanderbilt.edu.
David
D
Charles
Department of Neurosurgery, Vanderbilt University Medical Center, USA.
Peter E
PE
Konrad
Department of Neurosurgery, Vanderbilt University Medical Center, USA.
Joseph S
JS
Neimat
Department of Neurology, Vanderbilt University Medical Center, USA.
Anna L
AL
Molinari
Department of Psychiatry, Vanderbilt University Medical Center, USA.
Michael G
MG
Tramontana
Center for Healthcare Ethics, Cedars-Sinai Medical Center, USA.
Stuart G
SG
Finder
Stritch School of Medicine, Loyola University Chicago, USA.
Chandler E
CE
Gill
Kaiser Permanente Los Angeles Medical Center, USA.
Mark J
MJ
Bliton
Department of Neurosurgery, Vanderbilt University Medical Center, USA.
Chris
C
Kao
Department of Neurology, Vanderbilt University Medical Center, USA.
Fenna T
FT
Phibbs
Department of Neurology, Vanderbilt University Medical Center, USA.
Peter
P
Hedera
Department of Psychiatry, Vanderbilt University Medical Center, USA.
Ronald M
RM
Salomon
Walter Reed National Military Medical Center, USA.
Kevin R
KR
Cannard
Department of Biostatistics, Vanderbilt University Medical Center, USA.
Lily
L
Wang
Department of Biostatistics, Vanderbilt University Medical Center, USA.
Yanna
Y
Song
Department of Neurology, Vanderbilt University Medical Center, USA.
Thomas L
TL
Davis
D000368:Aged; D046690:Deep Brain Stimulation / Q000379:methods*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000175:diagnosis* / Q000503:physiopathology / Q000628:therapy*; D010865:Pilot Projects; D011446:Prospective Studies; D016037:Single-Blind Method; D020531:Subthalamic Nucleus / Q000502:physiology*
Deep brain stimulation; Parkinson's disease; Subthalamic nucleus