Cognitive outcome following staged bilateral pallidal stimulation for the treatment of Parkinson’s disease
Introduction
The popularity of neurosurgical treatments for the alleviation of parkinsonian symptoms diminished in the late 1960s upon the introduction of levodopa therapy. Observation of the limitations of pharmacotherapy, in conjunction with technological advances and the rediscovery by Laitinen [1], [2] of Leksell’s pallidotomy, prompted a resurgence in the interest of surgical treatments for refractory Parkinson’s disease [3], [4], [5], [6]. Numerous recent studies have confirmed pallidotomy’s success in alleviating tremor, bradykinesia and rigidity [7], [8], [9], [10], [11], [12], [13] and improving quality of life [14], [15], [16].
Although modern pallidotomy is considered to entail less cognitive morbidity than operations in the pre-levodopa era (but see Wilkinson and Tröster [17] for a review of difficulties in comparing outcomes in early and more recent patient series), the potential cognitive morbidity associated with even unilateral pallidotomy [18], [19], [20] has lead some to suggest that chronic deep brain stimulation (DBS) of the globus pallidus may provide a safer, more advantageous alternative to creating a permanent brain lesion. Potential advantages of DBS include the adjustability of stimulation parameters over time, setting of stimulation parameters to maximize motor benefits while minimizing adverse side effects (including speech and cognitive dysfunction), and the potential to benefit from drugs developed in the future.
Despite the belief that DBS is cognitively safer than ablation, virtually no reports empirically document the neurobehavioral safety of pallidal DBS (for review see Fields and Tröster [21]). Ghika and colleagues [22] found bilateral contemporaneous pallidal DBS to be relatively safe. Among their six cases, few significant or consistent neuropsychological changes were observed. Two patients showed improved recognition memory, but two showed decreased verbal fluency. Worsening of dysarthria was observed in one other patient. Because unilateral pallidal stimulation, although generally safe from a cognitive standpoint [23], [24], can also lead to decreased verbal fluency [23] and dysarthria [25], it is unclear from a study of contemporaneous bilateral stimulation whether implantation of the second electrode aggravates potential cognitive deficits after unilateral implantation, or whether such cognitive changes emerge only after the second pallidum is implanted. To this end, this study sought to study cognitive changes associated with a staged bilateral procedure, comparing cognitive functioning to baseline after unilateral implant, and again after a later bilateral implant.
Section snippets
Subjects
Six patients with refractory Parkinson’s disease underwent bilateral DBS. All were diagnosed with Parkinson’s disease based on two of three cardinal signs (tremor, bradykinesia, rigidity) and levodopa responsiveness. All had severe dyskinesias and motor fluctuations. Patients showing signs of dementia or psychiatric disturbances (with the exception of minor depression) were not eligible for study inclusion.
Surgical procedure
The neurological evaluation and surgical procedure has been described previously [26]. In
Results
Results of bilateral pallidal DBS on motor function have been described in a previous report [26]. Table 2 summarizes neuropsychological test results for individual patients, including raw scores (unless otherwise indicated) at each evaluation, as well as impairment status (impaired–not impaired) and observed change (standard deviation). A test score was considered to be impaired if: (1) the score fell below published impairment cutoffs, or (2) the score fell at or below 5th %ile, or (3) the
Discussion
In reviewing the patients’ performance as a group, few consistent changes in domains of neurobehavioral functioning appeared. Following unilateral surgery, significant performance improvements were observed in conceptualization and anxiety, with tendencies toward improvement in attention, delayed recall, and vigor. There were no significant performance decrements following unilateral surgery, but trends toward poorer performance were most likely to be observed in constructional abilities and
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