The major aim of this study is to carry out a controlled clinical trial of pallidotomy for the treatment of advanced intractable Parkinson's Disease (PD) and to comprehensively evaluate these patients for changes in motor, cognitive and psychiatric state. Two recent factors have led to a renewed interest in pallidotomy for PD: 1) the demonstration that lesions of the subthalamic nucleus (STN) in the experimental monkey model of PD ameliorates the cardinal signs of this disorders, including akinesia, and 2) the recent report that pallidotomy also that pallidotomy provides significant benefit to patients with PD who no longer derive adequate response to anti-parkinson medications and who suffer from motor fluctuations and drug-induced dyskinesias. At the present time pallidotomy is being performed with increasing frequency in ever more centers. As yet, however, there have been no-well controlled clinical trial of pallidotomy. We propose to carry out a controlled clinical trial of pallidotomy versus best medical therapy in 42 patients with intractable PD. Surgical patients and controls will be monitored for 3 months prior to surgery and every 6 months thereafter. Clinical evaluation will be carried out in the Clinical Research Center. We will perform comprehensive evaluations of motor, cognitive and psychiatric state pre and post operatively. The functional assessments include standard parkinsonian rating systems used for reevaluation of transplant patients as well as quantitative motor testing. Pallidotomy will be carried out under both MRI and microelectrode-guidance. Lesion size and placement will be determined post-operatively using new high resolution MRI imaging techniques. Changes in parkinsonian and behavioral signs will be correlated with lesion location. These studies will serve to: 1) validate the safety and efficacy of pallidotomy in PD, 2) better define the optimal target location and 3) provide important data on the effects of pallidal lesion on motor, cognitive and psychiatric functioning in parkinsonian patients.
