Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: comparison of pre- and postoperative neuropsychological evaluation
Introduction
Recently, it has been shown that deep brain stimulation (DBS) of the subthalamic nucleus (STN) [1], [2], [3], [4] and of the internal globus pallidus (GPi) [5], [6], [7], [8] is an effective therapy for advanced Parkinson's Disease (PD). The main clinical features of the advanced phase of the disease are represented by motor fluctuations (wearing offs, on–off phenomena) and levodopa-induced involuntary movements, with a difficult to achieve satisfactory quality of life through dopaminergic therapies [9], [10]. Bilateral STN DBS seems to be more effective with respect to bilateral GPi DBS and it allows a significant reduction of the amount of dopaminergic drugs with a consequent improvement of dyskinesias [4], [6], [11]. Moreover, the effects of STN DBS seem to persist in the long-term follow-up [12].
The principal advantages of the DBS procedures are the reversibility, the possibility to modify the stimulator parameters according to patients needs and the minor incidence of side effects [13]. The last one is relevant with respect to the lesioning procedures; in fact, it has been reported that unilateral pallidotomy can be responsible for cognitive impairment of patients, and a bilateral lesioning procedure of GPi greatly increases this risk [14]. However, the effects of DBS on cognitive functions are still little known; in particular, it is relevant to investigate whether the surgical procedure can negatively interfere with the cognitive performances or, on the contrary, whether the functional inhibition of a hyperactive target in PD can modify the non-motor basal ganglia-thalamo-cortical circuits with an effect on the cognitive processing.
A recent study [15] analysed a large series of PD patients who underwent bilateral implantation of stimulating electrodes in STN or GPi; a high percentage of patients were examined before and after surgery without levodopa, and all patients were assessed in the stimulation on condition after surgery. The main result was the lack of any significant cognitive side effects for both surgical procedures; the neuropsychological profile of the patients was unchanged after 3–6 months of STN or GPi DBS, except for a decrease in verbal fluency and an improvement in the Trail Making B test observed only in the patients implanted in the STN. In a successive study, an improvement in psychomotor speed (reaction times tasks, Trail Making, Stroop test) and in working memory was reported in STN-implanted patients evaluated in the stimulation on/medication on condition, while a mild category fluency deficit was observed in the stimulation on/medication off condition [16].
Others authors [14] suggested the presence of a cognitive decline of PD patients after bilateral STN DBS; in this case, the assessed pattern of neuropsychological modifications was similar to that observed in patients affected by progressive supranuclear palsy (PSP), and it was observed only in patients older than 69.
We studied 20 consecutive PD patients to verify whether bilateral STN DBS could be responsible for neuropsychological alterations.
Section snippets
Subjects
We studied 20 right-handed PD patients (12 men and 8 women) bilaterally implanted for STN DBS. The mean age of the patients at the time of the surgery was 61.6 years (6 SD); the mean duration of the illness was 15.4 years (4.9 SD), with a mean duration of the levodopa treatment of 14.3 years (5.2 SD). The mean Hoehn and Yahr [17] stage was 2.5 (0.3 SD) in the on phase and 4 (0.4 SD) in the off phase. The principal inclusion criteria for the surgical therapy were: (a) the presence of severe
Results
The STN DBS led to a significant improvement of the PD symptoms in all the patients. In Table 1, we reported the data relative to the UPDRS sub-scores in the four different conditions, the preoperative med on and med off, and the postoperative stim on/med off and stim on/med on.
Table 2(a) shows the findings relative to the memory analysis. All the tests (Rivermead, Spatial Learning, Paired Associate Learning, Corsi's Block Tapping and Bi-sillabic Words Repetition) showed no significant
Discussion
The effect of STN DBS on cognitive functions in PD patients is a relevant issue for the confirmation of the safety of this surgical treatment.
The most relevant finding of our study concerns the absence of an overall cognitive decline after the surgical procedure. The comparison between the med off, the med on, the stim on/med off and the stim on/med on conditions didn't show any significant difference for all the neuropsychological functions examined; the conditions of levodopa alone, surgical
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