Subthalamic Nucleus Stimulation in Parkinson's Disease: 5-Year Extension Study of a Randomized Trial.

BACKGROUND: In Parkinson's disease (PD) long-term motor outcomes of subthalamic nucleus deep brain stimulation (STN-DBS) are well documented, while comprehensive reports on non-motor outcomes are fewer and less consistent. OBJECTIVE: To report motor and non-motor symptoms after 5-years of STN-DBS. METHODS: We performed an open 5-year extension study of a randomized trial that compared intraoperative verification versus mapping of STN using microelectrode recordings. Changes from preoperative to 5-years of STN-DBS were evaluated for motor and non-motor symptoms (MDS-UPDRS I-IV), sleep disturbances (PDSS), autonomic symptoms (Scopa-Aut), quality of life (PDQ-39) and cognition through a neuropsychological test battery. We evaluated whether any differences between the two randomization groups were still present, and assessed preoperative predictors of physical dependence after 5 years of treatment using logistic regression. RESULTS: We found lasting improvement of off-medication motor symptoms (total MDS-UPDRS III, bradykinetic-rigid symptoms and tremor), on-medication tremor, motor fluctuations, and sleep disturbances, but reduced performance across all cognitive domains, except verbal memory. Reduction of verbal fluency and executive function was most pronounced the first year and may thus be more directly related to the surgery than worsening in other domains. The group mapped with multiple microelectrode recordings had more improvement of bradykinetic-rigid symptoms and of PDQ-39 bodily discomfort sub-score, but also more reduction in word fluency. Older age was the most important factor associated with physical dependence after 5 years. CONCLUSION: STN-DBS offers good long-term effects, including improved sleep, despite disease progression. STN-DBS surgery may negatively impact verbal fluency and executive function.

Subthalamic deep brain stimulation improves sleep and excessive sweating in Parkinson's disease.

Parkinson's disease (PD) is a complex multisystem disorder with motor and non-motor symptoms (NMS). NMS may have an even greater impact on quality of life than motor symptoms. Subthalamic nucleus deep brain stimulation (STN-DBS) has been shown to improve motor fluctuations and quality of life, whereas the effects on different NMS have been less examined. Sleep disturbances and autonomic dysfunction are among the most prevalent NMS. We here report the efficacy of STN-DBS on sleep disturbances and autonomic dysfunction. In the parent trial, 60 patients were included in a single-center randomized prospective study, with MDS-UPDRS III and PDQ-39 as primary endpoints at 12 months of STN-DBS. Preplanned assessments at baseline and postoperatively at 3 and 12 months also included Parkinson's Disease Sleep Scale (PDSS); Scopa-Aut; and MDS-UPDRS I, II, and IV. We found that STN-DBS had a significant and lasting positive effect on overall sleep quality, nocturnal motor symptoms and restlessness, and daytime dozing. Several aspects of autonomic dysfunction were also improved at 3 months postoperatively, although at 12 months only thermoregulation (sudomotor symptoms) remained significantly improved. We could not identify preoperative factors that predicted improvement in PDSS or Scopa-Aut. There was a close relationship between improved autonomic symptoms and improved quality of life after 1 year. NMS and especially sleep and autonomic dysfunction deserve more focus to improve patient outcomes further.

Multiple Microelectrode Recordings in STN-DBS Surgery for Parkinson's Disease: A Randomized Study.

BACKGROUND: Subthalamic nucleus deep brain stimulation improves motor symptoms and fluctuations in advanced Parkinson's disease, but the degree of clinical improvement depends on accurate anatomical electrode placement. Methods used to localize the sensory-motor part of the nucleus vary substantially. Using microelectrode recordings, at least three inserted microelectrodes are needed to obtain a three-dimensional map. Therefore, multiple simultaneously inserted microelectrodes should provide better guidance than single sequential microelectrodes. We aimed to compare the use of multiple simultaneous versus single sequential microelectrode recordings on efficacy and safety of subthalamic nucleus stimulation. METHODS: Sixty patients were included in this double-blind, randomized study, 30 in each group. Primary outcome measures were the difference from baseline to 12 months in the MDS-UPDRS motor score (part III) in the off-medication state and quality of life using the Parkinson's Disease Questionnaire-39 (PDQ-39) scores. RESULTS: The mean reduction of the MDS-UPDRS III off score was 35 (SD 12) in the group investigated with multiple simultaneous microelectrodes compared to 26 (SD 10) in the single sequential microelectrode group (p = 0.004). The PDQ-39 Summary Index did not differ between the groups, but the domain scores activities of daily living and bodily discomfort improved significantly more in the multiple microelectrodes group. The frequency of serious adverse events did not differ significantly. CONCLUSIONS: After 12 months of subthalamic nucleus stimulation, the multiple microelectrodes group had a significantly greater improvement both in MDS-UPDRS III off score and in two PDQ-39 domains. Our results may support the use of multiple simultaneous microelectrode recordings. TRIAL REGISTRATION: http://ClinicalTrials.gov Identifier: NCT00855621 (first received March 3, 2009).

Surgical site infections after deep brain stimulation surgery: frequency, characteristics and management in a 10-year period.

BACKGROUND/AIMS: Deep brain stimulation (DBS) implant infection is a feared complication, as it is difficult to manage and leads to increased patient morbidity. We wanted to assess the frequency and possible risk factors of DBS related infections at our centre. In the purpose of evaluating treatment options, we also analyzed treatment, and the clinical and microbiological characteristics of the infections. METHODS: Electronic medical records of all patients undergoing DBS surgery at our centre, from 2001 through 2010, were retrospectively reviewed. RESULTS: Of the 588 procedures performed 33 (5.6%) led to an infection. Some patients underwent several procedures, thus 32 out of totally 368 patients (8.7%), and 19 out of 285 patients (6.7%) who received primary lead implantation, developed an infection. Most infections (52%) developed within the first month and 79% within three months. In the majority of the infections (79%) hardware removal was performed. Staphylococcus aureus infections were the most frequent (36%), and more likely to have earlier onset, pus formation, a more aggressive development and lead to hardware removal. No risk factors were identified. CONCLUSIONS: Our results indicate that infections with more severe symptoms and growth of staphylococcus aureus should be treated with local hardware removal and antibiotic therapy. In other infections, an initial trial of antibiotic treatment could be considered. New knowledge about the microbiology of DBS related infections may lead to more effective antimicrobial treatment.

Long-term follow-up of thalamic deep brain stimulation for essential tremor - patient satisfaction and mortality.

BACKGROUND: Ventral intermediate thalamic nucleus (VIM) deep brain stimulation (DBS) is an effective treatment for tremor, but there is limited data on long-term efficacy and mortality after VIM-DBS. Here we report the analysis of patient satisfaction and mortality in all patients treated in our center 1996-2010 with VIM-DBS for essential tremor (ET). METHODS: Forty-six consecutive patients were included in this study. Medical records were reviewed, and a follow-up questionnaire was sent to all surviving patients. RESULTS: Seventy percent of all possible participants (26 patients) answered the questionnaire. Follow-up time for the responding patients was median 6.0 years (2-16). Median self-reported score on visual analogue scale of the initial postoperative effect on tremor was 8.5 (0.1-10), with a significant reduction to 7.4 (0-10) at follow-up (p = 0.001). Patients reported a median score of 10 (0-10) for overall patient satisfaction with VIM-DBS treatment. Eight patients (17%) died after median 8.9 years (0.6-15) after surgery, at median age 77.4 years (70-89). One patient (2%) committed suicide seven months after the operation. Calculated standard mortality ratio among ET patients was 1.3 (CI 0.6-2.6), similar to the general population. CONCLUSION: We found no significant increase in mortality in this cohort of VIM-DBS operated ET patients compared to the general population in Norway. The patients reported high long-term satisfaction and continuing effect of VIM-DBS on tremor even after many years. VIM-DBS therefore seems to be an effective symptomatic long-term treatment of ET. However, one patient committed suicide. Only one other suicide has previously been reported after VIM-DBS. It is therefore still unclear whether VIM-DBS increases suicide risk.