Neuropsychological consequences of chronic bilateral stimulation of the subthalamic nucleus in Parkinson's disease.

The aim of this study was to examine possible neuropsychological changes in patients with advanced idiopathic Parkinson's disease treated with bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN). Eleven patients (age = 67 +/- 8 years, years with Parkinson's disease = 15 +/- 3, verbal IQ = 114 +/- 12) were evaluated (in their best 'on state') with tests assessing processes reliant on the functional integrity of frontal striatal circuitry, prior to the procedure (n = 11), at 3-6 months (n = 11) and at 9-12 months (n =10) post-operatively. Six of these patients were older than 69 years. Despite clinical motor benefits at 3-6 months post-operative, significant declines were noted in working memory, speed of mental processing, bimanual motor speed and co-ordination, set switching, phonemic fluency, long-term consolidation of verbal material and the encoding of visuospatial material. Declines were more consistently observed in patients who were older than 69 years, leading to a mental state comparable with progressive supranuclear palsy. 'Frontal' behavioural dyscontrol without the benefit of insight was also reported by half (three of six) of the caregivers of the elderly subgroup. At 9-12 months postoperative, only learning based on multiple trials had recovered. Tasks reliant on the integrity of frontal striatal circuitry either did not recover or gradually worsened over time. Bilateral STN DBS can have a negative impact on various aspects of frontal executive functioning, especially in patients older than 69 years. Future studies will evaluate a larger group of patients and examine the possible reversibility of these effects by turning the DBS off.

Neuropsychologic assessment of patients for movement disorder surgery.

The neuropsychologic evaluation of patients under consideration for movement disorder surgery is recognized as being an essential component of the preoperative process. Patients with early-stage concomitant dementia must be identified and the relative risk of postoperative cognitive decline evaluated. Knowledge of the patterns of an individual's strengths and weaknesses might also be a factor in deciding on a neurosurgical procedure. Although the advent of pallidal deep brain stimulation (DBS) has possibly resulted in reduced risk of induced cognitive impairment, even this procedure has been associated with negative sequelae. DBS within the subthalamic nucleus is becoming the method of choice and this may lead to cognitive and behavioral compromise, especially in the elderly patient. The team considering the establishment of neurosurgical treatment is often at a loss to decide how much neuropsychologic testing is required to determine relative risks of cognitive or behavioral morbidity as a consequence of the procedure. A brief summary of expected outcome and of pertinent family process and psychodynamic issues are addressed. This article is intended to serve as a guide to permit clinicians to choose the appropriate length and depth of neuropsychologic assessment, but also to highlight the confounding factors often present in these patients.

Neuropsychological outcome of GPi pallidotomy and GPi or STN deep brain stimulation in Parkinson's disease.

This paper highlights the neuropsychological sequelae of posteroventral pallidotomy (PVP) and deep brain stimulation (DBS) of the subthalamic nucleus (STN) and the internal segment of the globus pallidus (GPi) at 3/6 months postoperatively. Results are based on our extensive experience with PVP and our preliminary observations with DBS. Patients with borderline cognitive or psychiatric functioning risk postoperative decompensation. Nonlateralizing attentional and hemisphere-specific impairments of frontostriatal cognitive functions followed unilateral PVP. "Frontal" behavioral dyscontrol was observed in approximately 25% of patients. Three cases of staged bilateral PVP suggest that premorbid factors may predict outcome, although lesion size and location are also critical. Older patients are at risk for significant cognitive and behavioral decline after bilateral STN DBS, while GPi DBS may be safer.

Relationship of lesion location to cognitive outcome following microelectrode-guided pallidotomy for Parkinson's disease: support for the existence of cognitive circuits in the human pallidum.

Current models of basal ganglia anatomy posit the existence of multiple parallel, anatomically segregated circuits. Anatomical data from non-human primates suggest that the circuits subserving motor functions are segregated from those subserving cognitive functions. Here we present data that demonstrate that, in humans, motor and cognitive frontosubcortical circuits are segregated. We studied a group of patients with Parkinson's disease undergoing surgical lesioning of the globus pallidus internus for relief of their symptoms. Lesion location along an anteromedial-to-posterolateral axis was found to be related to postsurgical outcome on both cognitive and motor measures. Performance on several neuropsychological measures, including the generation of category exemplars and continuous mental addition, was linearly related to distance along this axis, with anteromedial lesions leading to postsurgical impairment, intermediate lesions having little effect and posterolateral lesions leading to an improvement on several measures. The same relationship was found between memory performance under conditions of proactive interference and lesion location within the globus pallidus internus. In contrast, bradykinesia, assessed as the speed of finger-tapping, had a non-linear relationship to lesion location, intermediate lesions leading to greater postsurgical improvement than lesions in more extreme anteromedial or posterolateral locations. These data demonstrate that the cognitive effects of pallidotomy can be dissociated from the motor effects. These effects depend upon the placement of the lesions within the globus pallidus internus, supporting the segregation of functionally distinct circuits in the human pallidum.

Neuropsychological consequences of posteroventral pallidotomy for the treatment of Parkinson's disease.

OBJECTIVE: Neuropsychological changes were assessed in patients who had idiopathic PD after unilateral posteroventral pallidotomy. METHODS: Posteroventral stereotactic pallidotomies were performed on 42 PD patients (24 right and 18 left hemisphere). All patients were evaluated in the "on state" before the procedure (n = 42) and at intervals of 3 (n = 26), 6 (n = 27), and 12+ (n = 24) months after surgery. RESULTS: Modest improvement in sustained attention and decline in working memory was observed by 6 months after surgery. Left hemisphere lesions led to a loss of verbal learning (-2.2 SD) and verbal fluency (-1.6 SD) in 60% of patients at their first evaluation at 3 or 6 months. No patients returned to baseline on the verbal fluency task and most (71%) did not recover verbal-learning ability by 12 months after surgery. Right hemisphere lesions led to a loss of visuospatial constructional abilities (-3.5 SD), which fully resolved by 12 months for all but one patient. Evidence of further decline of frontal-executive functioning was noted within other tasks but not on a "direct" test (i.e., Conditional Associative Learning). Lastly, behavioral changes of a "frontal nature" were reported in 25% to 30% of patients. These cognitive and emotional costs increased dependence in these domains and negatively affected some patients' relations with caregivers and restricted their ability to function properly at work or in social settings. Caregivers, particularly, and patients who were aware of their resulting changes had difficulty adjusting after surgery. CONCLUSIONS: Although patients and caregivers were generally pleased with the clinical neurologic outcome of the procedure, the neurologic benefits of unilateral pallidotomy must be weighed against modest cognitive and behavioral risks.