ReviewBehavioural changes after bilateral subthalamic stimulation in advanced Parkinson disease: A systematic review
Introduction
Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN), once considered an experimental treatment, is nowadays widely performed in the treatment of advanced Parkinson disease (PD). Many studies have appeared on the short-term effects [1], [2], [3], [4], [5], [6], [7], [8], [9], [10]. More recently, four-year [11], [12] and 5 year follow-up [13] effects were reported. Bilateral STN stimulation induced a marked improvement in motor function while off medication and in dyskinesia while on medication. These results reinforce the value of bilateral STN DBS in the long-term treatment of advanced Parkinson disease. On the other hand, STN DBS is accompanied by a new set of side effects and complications, which may occur at any time from surgery to several years postoperatively [14], [15]. These negative effects can be related to the hardware such as infections [14], lead fracture [16], dislocation [17], to the electrode insertion (bleedings) or specifically to the region stimulated [18], [19], [20], [21], [22].
In several case reports and small case series, behavioural changes following STN DBS have been described such as mania [18], [19], [23], [24], depression [6], [10], [13], [21], [22], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37] and cognitive alterations [6], [15], [20], [24], [29], [30], [38], [39], [40], [41], [42]. On the other hand, other authors did not find any negative effect of STN DBS on behaviour [43], [44], [45], [46], [47]. There is an ongoing debate about which specific behavioural changes are related to bilateral STN DBS and to what extent these occur. In the present study, our aim was to systematically analyse these side-effects in reports describing original data on bilateral STN stimulation in advanced PD.
Section snippets
Search strategy
A structured Medline (Pubmed) search was performed in articles published up until June 2004, using previously described search methods [48], [49], [50]. The following key words were used: STN, subthalamic nucleus, subthalamic in combinations with DBS, deep brain stimulation, stimulation, HFS, high frequency stimulation. These studies were reviewed independently by three investigators (YT, ST and AT).
Study selection and data extraction
Studies were selected according to the following criteria. Preclinical studies and reviews not
Patient characteristics
In total, 1398 patients were implanted with bilateral electrodes at the level of the STN. The male female ratio was 3:2 (Table 1). The mean age of the total population at the time of surgery was 55 years (95% CI 41–68) with a mean disease duration of 11 years (95% CI 4–19). The mean follow-up duration was 13 months (95% CI 4–21), and the cumulative follow-up period was 1480 patient-years in the study group.
Effects of bilateral STN DBS on UPDRS subscores
The mentation, behaviour and mood score (Part I) of the unified Parkinson disease rating
Discussion
In the present review, we systematically analyzed patient characteristics, surgical technique, motor outcome and behavioural changes in patients who had undergone bilateral STN DBS for advanced PD. Our results point out that despite substantial improvement of motor disability, patients undergoing bilateral STN DBS can experience different behavioural changes. Three important behavioural changes could be determined. These are cognitive dysfunctions noticed in 41% of the patients, depression in
Conclusion
The results of our study confirm that STN DBS is a very effective in alleviating PD symptoms. It is associated by behavioural changes of which cognitive dysfunctions and emotional changes are the most frequent. Patients with preoperative clinically relevant behavioural alterations can be at risk for further deterioration after surgery. Patients who are candidates fro STN DBS should be subjected to a risk/benefit evaluation. For some patients, an alternative could be GPi DBS, in the case
Acknowledgements
The present study was funded by the Dutch Medical Research Council, grant no.: 940-37-027 and the Dutch Brain Foundation grant nos: 10F02.13, 10F03.19, and 10F04.17.
Authors'contribution. YT, ST and AT carried out the search. YT, PB and VVV wrote this review together, YT produced the tables, AK performed the statistical analysis. All authors reviewed and revised the text.
Conflict of interest. The authors have not received any grants from (potential) sponsors or supporting companies.
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