The major aim of this study is to carry out a prospective, randomized clinical trial of deep brain stimulation (DBS) in the internal segment of the globus pallidus (GPi) and subthalamic nucleus (STN) for the treatment of advanced Parkinson's disease (PD). Medical therapy is the mainstay of treatment for patients with PD. After several years of drug therapy, however, a large proportion of patients experience worsening of their parkinsonism and develop incapacitating motor fluctuations and dyskinesias. To deal with this, attention has been directed to surgical procedures, especially ablative therapies, e.g. pallidotomy, and more recently deep brain stimulation (DBS). DBS mimics the effects of ablation, but is reversible. It also has the advantage in that one can adjust stimulation parameters to physiologically change the area of inactivation and to implant both sides without the high incidence of complications associated with bilateral pallidotomy. In recent years DBS in the STN and GPi has been explored in pilot studies for the treatment of patients with advanced PD. Only a few nonrandomized studies examining the effect of DBS in the STN and GPi have been performed, however, and the results, although promising, have been highly variable. This study, which follows upon our current NIH supported randomized clinical trial of pallidotomy versus medical management for PD, will comprehensively evaluate the effects of DBS in GPi and STN on motor, neuropsychological and psychiatric function, and quality of life in patients with PD. The current proposal offers the unique opportunity of using the current cohort of patients in the pallidotomy for PD clinical trial for comparison to DBS. This study will address three key issues: 1) whether there are significant differences between GPi-DBS, STN-DBS and GPi pallidotomy. 2) which patients are the best candidates for DBS and 3) whether bilateral stimulation (GPi or STN) is superior to combined GPi pallidotomy and DBS. Overall, these studies will provide important data on the short and long term effects of DBS in the STN and GPi on motor, cognitive and psychiatric functioning and quality of life in parkinsonian patients and provide much needed guidelines regarding patient selection and optimal surgical approach.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Special Emphasis Panel (ZRG1-BDCN-2 (03))
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Moy, Claudia S
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Cleveland Clinic Lerner
Internal Medicine/Medicine
Schools of Medicine
United States
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Alberts, Jay L; Hallahan, Katie; Thota, Anil et al. (2010) Reducing cognitive-motor declines associated with bilateral subthalamic deep brain stimulation through computational modelling in a Parkinson's disease patient. J Neurol Neurosurg Psychiatry 81:1170-2
McIntyre, Cameron C; Frankenmolle, Anneke M; Wu, Jennifer et al. (2009) Customizing deep brain stimulation to the patient using computational models. Conf Proc IEEE Eng Med Biol Soc 2009:4228-9
Alberts, Jay L; Hass, Christopher J; Vitek, Jerrold L et al. (2008) Are two leads always better than one: an emerging case for unilateral subthalamic deep brain stimulation in Parkinson's disease. Exp Neurol 214:1-5
Alberts, J L; Okun, M S; Vitek, J L (2008) The persistent effects of unilateral pallidal and subthalamic deep brain stimulation on force control in advanced Parkinson's patients. Parkinsonism Relat Disord 14:481-8
Alberts, Jay L; Voelcker-Rehage, Claudia; Hallahan, Katie et al. (2008) Bilateral subthalamic stimulation impairs cognitive-motor performance in Parkinson's disease patients. Brain 131:3348-60