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Background: Deep brain stimulation (DBS) improves motor symptoms in Parkinson's disease (PD), but questions remain regarding neuropsychological decrements sometimes associated with this treatment, including rates of statistically and clinically meaningful change, and whether there are differences in outcome related to surgical target., Methods: Neuropsychological functioning was assessed in patients with Parkinson's disease (PD) at baseline and after 6 months in a prospective, randomised, controlled study comparing best medical therapy (BMT, n=116) and bilateral deep brain stimulation (DBS, n=164) at either the subthalamic nucleus (STN, n=84) or globus pallidus interna (GPi, n=80), using standardised neuropsychological tests. Measures of functional outcomes were also administered., Results: Comparison of the two DBS targets revealed few significant group differences. STN DBS was associated with greater mean reductions on some measures of processing speed, only one of which was statistically significant in comparison with stimulation of GPi. GPi DBS was associated with lower mean performance on one measure of learning and memory that requires mental control and cognitive flexibility. Compared to the group receiving BMT, the combined DBS group had significantly greater mean reductions at 6-month follow-up in performance on multiple measures of processing speed and working memory. After calculating thresholds for statistically reliable change from data obtained from the BMT group, the combined DBS group also displayed higher rates of decline in neuropsychological test performance. Among study completers, 18 (11%) study participants receiving DBS displayed reliable decline by multiple indicators in two or more cognitive domains, a significantly higher rate than in the BMT group (3%). This multi-domain cognitive decline was associated with less beneficial change in subjective ratings of everyday functioning and quality of life (QOL). The multi-domain cognitive decline group continued to function at a lower level at 24-month follow-up., Conclusions: In those with PD, the likelihood of significant decline in neuropsychological functioning increases with DBS, affecting a small minority of patients who also appear to respond less optimally to DBS by other indicators of QOL., Trial Registration Number: NCT00056563 and NCT01076452., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To evaluate the long-term effects of deep brain stimulation (DBS) on quality of life (QOL) in therapy-refractory obsessive-compulsive disorder (OCD) patients., Design: 16 patients who met Diagnostic and Statistical Manual of Mental Disorders (4th ed) (DSM-IV) criteria for OCD and were considered therapy-refractory were treated with DBS. Patients were assessed 1 month before device implantation (T0), at 8 months of active stimulation (T1) and at 3-5 years of active stimulation (T2). QOL was measured with the WHO Quality of Life Scale-Brief Version (WHOQOL-BREF) that covers physical, psychological, social and environmental domains. The study was conducted between April 2005 and January 2011 at the Academic Medical Center, Amsterdam, The Netherlands., Results: At T1 and T2, we found significant improvement (p<0.05) in the general score and in the physical, psychological and environmental domains of WHOQOL-BREF. Between T1 and T2, the physical and psychological domains improved further (p<0.05). At T2, the general score improved by a total of 90%, the physical and psychological domains both improved by 39.5% and the environmental domain improved by 16%. The social domain did not change between baseline and follow-up assessments., Conclusions: In line with symptom improvement, patient's QOL improved in the general score and in three of the four WHOQOL-BREF domains. This suggests that the improvement caused by DBS is not limited to symptom reduction alone, but also has a positive influence on patients' perception of their physical, psychological, environmental and global QOL., Clinical Trial Registration: http://isrctn.org identifier: ISRCTN23255677.

Background: The subthalamic nucleus (STN) is an efficient target for treating patients with Parkinson's disease as well as patients with obsessive-compulsive disorder (OCD) using high frequency stimulation (HFS). In both Parkinson's disease and OCD patients, STN-HFS can trigger abnormal behaviours, such as hypomania and impulsivity., Methods: To investigate if this structure processes emotional information, and whether it depends on motor demands, we recorded subthalamic local field potentials in 16 patients with Parkinson's disease using deep brain stimulation electrodes. Recordings were made with and without dopaminergic treatment while patients performed an emotional categorisation paradigm in which the response varied according to stimulus valence (pleasant, unpleasant and neutral) and to the instruction given (motor, non-motor and passive)., Results: Pleasant, unpleasant and neutral stimuli evoked an event related potential (ERP). Without dopamine medication, ERP amplitudes were significantly larger for unpleasant compared with neutral pictures, whatever the response triggered by the stimuli; and the magnitude of this effect was maximal in the ventral part of the STN. No significant difference in ERP amplitude was observed for pleasant pictures. With dopamine medication, ERP amplitudes were significantly increased for pleasant compared with neutral pictures whatever the response triggered by the stimuli, while ERP amplitudes to unpleasant pictures were not modified., Conclusions: These results demonstrate that the ventral part of the STN processes the emotional valence of stimuli independently of the motor context and that dopamine enhances processing of pleasant information. These findings confirm the specific involvement of the STN in emotional processes in human, which may underlie the behavioural changes observed in patients with deep brain stimulation.

Objective: To study patients' expectations of subthalamic deep brain stimulation (STN-DBS) and their subjective perceived outcome, by using qualitative and quantitative methods in Parkinson's disease (PD)., Methods: PD patients were prospectively examined before and 3 months after surgery. Semistructured interviews regarding preoperative expectations and postsurgical subjective perceived outcome were conducted. These were analysed using content analysis. For statistical analyses, patients were classified according to their subjective perceived outcome, resulting in three different subjective outcome groups (negative, mixed, positive outcome). The groups were used for multiple comparisons between and within each group regarding motor impairment, quality of life (QoL), neuropsychiatric status and cognitive functioning, using standard instruments. A logistic regression analysis was conducted to find predictors of subjective negative outcome. Receiver operating characteristic curves were used to analyse cut-off scores for predictive tests., Results: Of the 30 PD patients participating, 8 had a subjective negative outcome, 8 a mixed and 14 a positive outcome. All groups significantly improved in motor functioning. Patients with subjective negative outcome were characterised by preoperative unrealistic expectations, no postsurgical improvement in QoL, and significantly higher presurgical and postsurgical apathy and depression scores. Higher preoperative apathy and depression scores were significant predictors of negative subjective outcome. Cut-off scores for apathy and depression were identified., Conclusions: The mixed-method approach proved useful in examining a patient's subjective perception of STN-DBS outcome. Our results show that significant motor improvement does not necessarily lead to a positive subjective outcome. Moreover, PD patients should be screened carefully before surgery regarding apathy and depression. (DRKS-ID: DRKS00003221).

Background: Levodopa therapy in Parkinson's disease (PD) is associated with non-motor complications resulting from sensitisation of the ventral striatum system. Recent studies showed an improvement in non-motor complications in PD patients with subthalamic stimulation. We hypothesised that ventral striatum desensitisation might contribute to this improvement., Methods: Psychostimulant effects of levodopa were prospectively assessed in 36 PD patients with an acute levodopa challenge, before and 1 year after chronic subthalamic stimulation, using the Addiction Research Centre Inventory euphoria subscale. Postoperative evaluation was performed with the same dose of levodopa used in the preoperative assessment and after switching off stimulation. Preoperative and postoperative non-motor fluctuations in everyday life were investigated with the Ardouin Scale. Furthermore, in order to artificially reproduce non-motor fluctuations, a levodopa challenge keeping subthalamic stimulation on was performed to assess depression, anxiety and motivation before and after surgery under the different medication conditions., Results: After 1 year of chronic subthalamic stimulation with 60.3% reduction in dopaminergic medication, the acute psychostimulant effects of levodopa were significantly reduced compared with preoperatively, as measured by the euphoria subscale (7.22 ± 4.75 vs 4.75 ± 5.68; p = 0.0110). On chronic subthalamic stimulation and with markedly reduced dopaminergic medication, non-motor fluctuations were significantly improved. While off medication/on stimulation scores of depression and anxiety were improved, in the on medication/on stimulation condition the motivation score worsened., Conclusions: Acute psychostimulant effects of levodopa (off stimulation) were significantly reduced 1 year after surgery. These findings are likely due to desensitisation of the ventral striatum, allowed by the reduction of dopaminergic treatment, and the replacement of pulsatile treatment with continuous subthalamic stimulation.

Objective: Advanced Parkinson's disease (PD) is associated with various motor and non-motor symptoms which adversely impact health-related quality of life (HRQoL). Subthalamic nucleus (STN) deep brain stimulation (DBS) has been reported to improve some dimensions of HRQoL in appropriately selected candidates. Prior studies of HRQoL following DBS have used instruments comprising a predetermined list of questions which assess issues that are generally relevant in PD, but that may not be of equal or consistent importance to all individuals. In this study, we evaluate the effect of STN DBS on quality of life using the QLS(M), a modular questionnaire in which satisfaction scores for each item are weighted in light of patient-rated importance., Methods: We prospectively analysed QLS(M) scores in 21 patients with PD (11 men, mean age 61.5+/-8.6 years) before STN DBS surgery and at a mean 7.4+/-1.5, and again at a mean 16.6+/-6.8 months postoperatively., Results: Following STN DBS, patients experienced an improvement in HRQoL as measured by various items of the movement disorder and health modules of the QLS(M). Specifically, QLS(M) items pertaining to energy level/enjoyment of life, independence from help, controllability/fluidity of movement and steadiness when standing and walking showed significant improvements, although items concerning general life issues (eg, occupational function, interpersonal relationships, leisure activities) did not improve., Conclusion: Following STN DBS, symptomatic and functional improvements translate into higher HRQoL, with high satisfaction in domains related to movement disorders and general health.