Articles Neuropsychological and psychiatric sequelae of pallidotomy for PD Clinical trial findings J. Green, PhD; W.M. McDonald, MD; J.L. Vitek, MD, PhD; M. Haber, PhD; H. Barnhart, PhD; R.A.E. Bakay, MD; M. Evatt, MD; A. Freeman, MD; N. Wahlay, MPH; S. Triche, RN, MSN; B. Sirockman, BS; and M.R. DeLong, MD Abstract—Objective: To evaluate the neuropsychological and psychiatric sequelae of unilateral posterior pallidotomy for treatment of PD. Methods: Patients with idiopathic PD completed baseline and 3- and 6-month assessments after random assignment to an immediate surgery (n = 17) or medical management (n = 16) group. Results: Compared with the medical management group, the immediate surgery group with single lesions centered on the posterior internal pallidum showed superior naming and response inhibition, better verbal recall at 6 months, but greater distractibility, a tendency toward lower phonemic fluency, and a transient (3 months’ only) semantic fluency deficit. The group with left lesions had more neuropsychological deficits than the group with right lesions or the medical management group, although these occurred mainly at 3 (but not 6) months. At 6 months, the patients with left lesions showed better verbal memory retention than the patients with right lesions. On most measures, the pattern of individual clinical change did not differ as a function of surgery or lesion laterality, with the exception of a higher frequency of decline in phonemic fluency in the patients with left lesions at 6 months. Although psychiatric status did not change overall, a history of depression tended to increase the risk of a depressive episode following surgery. Conclusions: Well-targeted, uncomplicated, unilateral pallidotomy does not produce overall neuropsychological or psychiatric change, although there are subtle changes on specific measures sensitive to frontal lobe function. NEUROLOGY 2002;58:858 –865 Posterior pallidotomy, the lesioning of the posterior portion of the internal globus pallidus (GPi) to re- lieve symptoms of PD, 1 is not expected to have a major impact on cognitive and emotional behaviors modulated by the “associative” and “limbic” circuits that engage more anterior and medial portions of the GPi. 2 Comparisons of neuropsychological and psychi- atric performance before and after pallidotomy have generally reported minimal or no change. 3-9 The interpretation of previous studies, however, remains problematic for the following reasons. Most of the existing studies have not included a randomly assigned patient control group, making it difficult to determine the extent to which the observed changes are related to the surgical procedure or to uncon- trolled variables such as practice effects of repeated testing or disease progression. Also, the time course and magnitude of surgically related neuropsycholog- ical and psychiatric changes have not been well doc- umented. Finally, it is often unclear to what extent neuropsychological findings are related to single le- sions centered in the sensorimotor GPi. 10 This article details the neuropsychological and psychiatric data that were secondary outcome mea- sures in a clinical trial of posterior pallidotomy. Pa- tients were randomly assigned to either an immediate surgery (IS) group or to a patient control group treated with optimized medical management (MM). Patients were assessed at 3 and 6 months following surgery, and data were reanalyzed to ex- amine the impact of the few lesions that occurred outside of the sensorimotor GPi. The motor findings of the clinical trial have been submitted for publica- tion elsewhere. 11 Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Con- tents for the March 26 issue to find the title link for this article. From the Departments of Neurology (Drs. Green, Vitek, Evatt, Freeman, and DeLong, and S. Triche and B. Sirockman), Psychiatry (Dr. McDonald) and Neurosurgery (Dr. Bakay), Emory University School of Medicine, and Department of Biostatistics (Drs. Haber and Barnhart, and N. Wahlay), Rollins School of Public Health, Emory University, Atlanta, GA. Supported by NIH grant NS-32047 and Emory University Alzheimer’s Disease Center, NIA grant AG-10130. Received October 31, 2000. Accepted in final form November 30, 2001. Address correspondence and reprint requests to Dr. Joanne Green, Emory University, Department of Neurology, Wesley Woods Center, 1841 Clifton Road, Atlanta, GA 30329; e-mail: jgreen@emory.edu 858 Copyright © 2002 by AAN Enterprises, Inc.