Schuepbach WM, Rau J, Knudsen K, et al. Neurostimulation for Parkinson's disease with early motor complications

Assistance Publique–Hôpitaux de Paris, Centre d'Investigation Clinique (CIC) 9503, Institut du Cerveau et de la Moelle Épinière, Département de Neurologie, Université Pierre et Marie Curie–Paris 6 and INSERM, Centre Hospitalier Universitaire (CHU) Pitié–Salpêtrière, Paris, France.
New England Journal of Medicine (Impact Factor: 55.87). 02/2013; 368(7):610-22. DOI: 10.1056/NEJMoa1205158
Source: PubMed


Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinson's disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at an earlier stage of Parkinson's disease.
In this 2-year trial, we randomly assigned 251 patients with Parkinson's disease and early motor complications (mean age, 52 years; mean duration of disease, 7.5 years) to undergo neurostimulation plus medical therapy or medical therapy alone. The primary end point was quality of life, as assessed with the use of the Parkinson's Disease Questionnaire (PDQ-39) summary index (with scores ranging from 0 to 100 and higher scores indicating worse function). Major secondary outcomes included parkinsonian motor disability, activities of daily living, levodopa-induced motor complications (as assessed with the use of the Unified Parkinson's Disease Rating Scale, parts III, II, and IV, respectively), and time with good mobility and no dyskinesia.
For the primary outcome of quality of life, the mean score for the neurostimulation group improved by 7.8 points, and that for the medical-therapy group worsened by 0.2 points (between-group difference in mean change from baseline to 2 years, 8.0 points; P=0.002). Neurostimulation was superior to medical therapy with respect to motor disability (P<0.001), activities of daily living (P<0.001), levodopa-induced motor complications (P<0.001), and time with good mobility and no dyskinesia (P=0.01). Serious adverse events occurred in 54.8% of the patients in the neurostimulation group and in 44.1% of those in the medical-therapy group. Serious adverse events related to surgical implantation or the neurostimulation device occurred in 17.7% of patients. An expert panel confirmed that medical therapy was consistent with practice guidelines for 96.8% of the patients in the neurostimulation group and for 94.5% of those in the medical-therapy group.
Subthalamic stimulation was superior to medical therapy in patients with Parkinson's disease and early motor complications. (Funded by the German Ministry of Research and others; EARLYSTIM number, NCT00354133.).

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Available from: Günther Deuschl, Oct 06, 2015
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    • "This is in line with a recent study that failed to change physical activity behavior with an intervention directly targeting this issue [37]. Since a previous study demonstrated that PD patients exhibit the same level of physical activity as healthy elderly individuals at the onset of motor symptoms [25], targeting that behavior earlier in the course of the disease or performing the surgical intervention sooner [39] could then be beneficial to the patients' physical activity behavior and QoL. It is also possible that non-motor factors could contribute to sustained limitation of physical activity behavior after STN DBS in PD patients. "
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    ABSTRACT: Background: Maintaining a physically active lifestyle promotes general health. Recent studies have demonstrated that patients with Parkinson's disease (PD) fail to meet the suggested levels of physical activity and that targeted interventions do not always improve this behavior. One validated treatment for motor symptoms in PD is subthalamic stimulation (STN DBS). Objective: Assess whether motor symptom improvement following STN DBS translated into increased physical activity behavior. Methods: Twenty-two patients with PD scheduled for STN DBS filled-out the Phone-FITT physical activity questionnaire and the SF-36 quality of life questionnaire prior to surgery and 6 to 9 months postoperatively. Data were compared to age- and gender-matched healthy controls. Results: Our results demonstrate that PD patients' quality of life is significantly lower than healthy controls. While STN DBS improves motor symptoms in the intermediate term, it only improves some aspects of quality of life related to physical function. Furthermore, STN DBS did not modify physical activity behavior measured by the Phone-FITT, whether for household or recreational activities. Conclusion: The current study demonstrates that the motor improvements observed after STN DBS do not lead to systematic improvements in all aspects of quality of life or increased levels of physical activity. This highlights the need to develop and implement intervention strategies to promote an active lifestyle in this population, even if clinical improvement is evident following surgery.
    Journal of Parkinson's Disease 10/2014; 5(1). DOI:10.3233/JPD-140426 · 1.91 Impact Factor
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    • "Significant interest has evolved regarding the possibility of implanting DBS earlier in the disease course [6e9]. A recent study focused on implanting patients with mid-stage PD indicates that the combination of DBS and oral medications is superior to oral medications alone when DBS is applied after the onset of motor fluctuations [7] [9]. Application of the therapy in early disease, before quality of life and functional independence are compromised, may yield superior clinical benefit and delay functional decline [6]. "
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    ABSTRACT: Background Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson’s disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Methods Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50-75, on medication ≥ 6 months but < 4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n=15) or DBS+ODT (n=15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. Results As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. The DBS+ODT group took less medication at all time points, and this reached maximum difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS+ODT group suffered serious adverse events; remaining adverse events were mild or transient. Conclusions This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD.
    Parkinsonism & Related Disorders 07/2014; 20(7). DOI:10.1016/j.parkreldis.2014.03.019 · 3.97 Impact Factor
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    • "Preselection criteria were patients aged 50–75 who had been on medication between 6 and 48 months, free of motor fluctuations such as levodopa associated dyskinesias or unexpected “on/off” phenomena. These patients were earlier stage than in a previous study of DBS in patients with early motor fluctuations (8). After informed consent was obtained, patients underwent a detailed screening evaluation to ensure their eligibility for the trial. "
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    ABSTRACT: Patients with Parkinson's disease (PD) experience progressive neurological decline, and future interventional therapies are thought to show most promise in early stages of the disease. There is much interest in therapies that target the subthalamic nucleus (STN) with surgical access. While locating STN in advanced disease patients (Hoehn-Yahr Stage III or IV) is well understood and routinely performed at many centers in the context of deep brain stimulation surgery, the ability to identify this nucleus in early-stage patients has not previously been explored in a sizeable cohort. We report surgical methods used to target the STN in 15 patients with early PD (Hoehn-Yahr Stage II), using a combination of image guided surgery, microelectrode recordings, and clinical responses to macrostimulation of the region surrounding the STN. Measures of electrophysiology (firing rates and root mean squared activity) have previously been found to be lower than in later-stage patients, however, the patterns of electrophysiology seen and dopamimetic macrostimulation effects are qualitatively similar to those seen in advanced stages. Our experience with surgical implantation of Parkinson's patients with minimal motor symptoms suggest that it remains possible to accurately target the STN in early-stage PD using traditional methods.
    Frontiers in Neurology 03/2014; 5:25. DOI:10.3389/fneur.2014.00025
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