Ten-Year Outcome of Subthalamic Stimulation in Parkinson Disease

Clinica Neurologica, Università degli Studi di Perugia, Perugia, Italy.
Archives of neurology (Impact Factor: 7.42). 08/2011; 68(12):1550-6. DOI: 10.1001/archneurol.2011.182
Source: PubMed


To assess the 10-year motor outcome of deep brain stimulation of the subthalamic nucleus (STN-DBS) in patients with Parkinson disease (PD).
Patients with PD with bilateral STN-DBS were assessed according to the Core Assessment Program for Surgical Interventional Therapies in Parkinson's Disease protocol and videotaped at baseline and 1, 5, and 10 years after surgery. An independent rater blinded to stimulation and medication condition scored the 10-year video assessments.
Movement Disorders Centre, Toronto Western Hospital, University Health Network, University of Toronto.
Eighteen patients with advanced PD and 10-year follow-up of STN-DBS.
Bilateral STN-DBS surgery.
The primary outcome was the change in blinded Unified Parkinson's Disease Rating Scale (UPDRS) motor scores/subscores between the no medication/stimulation condition vs the no medication/no stimulation condition at 10 years. Secondary outcomes were the changes in blinded UPDRS motor scores between the medication/no stimulation and medication/stimulation conditions, UPDRS II scores, UPDRS IV dyskinesia and motor fluctuations scores, and anti-PD medication dose (levodopa equivalent daily dose) at different points.
In the 18 patients available for follow-up at 10 years, STN-DBS still significantly improved the UPDRS total motor score (P = .007) and resting and action tremor (P < .01 and P = .02, respectively) and bradykinesia (P = .01) subscores. The UPDRS II scores in the medication and no medication conditions, UPDRS IV dyskinesia and motor fluctuations scores, and the levodopa equivalent daily dose were also significantly reduced compared with baseline. Axial signs showed the most progressive decline in stimulation and levodopa response over the years.
This class III study provides evidence that stimulation-induced motor improvement was sustained overall at 10 years, although part of the initial benefit wore off mainly because of progressive loss of benefit on axial signs over time.

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    • "Specifically, the course of the total score and appendicular motor signs can be described as a linear function with an almost parallel decline in the Med-OFF/Stim-ON and Med-ON/Stim-ON condition and a slope that is similar to prior descriptions in patients with and without DBS [11]. In contrast to the expected progression of the disease, we confirmed previous findings of a stable state of the Med-OFF/Stim-OFF condition over time, which may result from too short interval between discontinuing stimulation and clinical evaluation [2] [3]. "
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    ABSTRACT: This study was conducted to better understand the development of clinical efficacy and impedance levels in the long-term course of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD). In this retrospective study of twenty PD patients, the motor part of the Unified Parkinson's Disease Rating Scale was periodically assessed i) after withdrawal of medication and inactivated stimulation, ii) after withdrawal of medication with activated stimulation and iii) after challenge with l-Dopa during activated stimulation up to 13 years after surgery. STN-DBS with or without medication significantly improved motor function up to 13 years after surgery. The contribution of axial symptoms increased over time. While the stimulation parameters were kept constant, the therapeutic impedances progressively declined. STN-DBS in PD remains effective in the long-term course of the disease. Constant current stimulation might be preferable over voltage-controlled stimulation, as it would alleviate the impact of impedance changes on the volume of tissue activated. Copyright © 2015. Published by Elsevier Ltd.
    No preview · Article · Jul 2015 · Parkinsonism & Related Disorders
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    • "There is one report indicating that STN DBS is neuroprotective, or has disease- modifying effects, although this is a topic that is highly debated in the field [3]. If disease modification does occur as a result of DBS, we know that it must be minimal, as PD is known to progress despite DBS [33], [34]. If disease modification did occur on a small scale, our hypothesis would be that it is achieved, at least in part, due to the proliferative effect of the electrical stimulation in the NSC/precursor cell compartment in the adult brain. "
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    ABSTRACT: Deep brain stimulation (DBS) has been used for more than a decade to treat Parkinson's disease (PD); however, its mechanism of action remains unknown. Given the close proximity of the electrode trajectory to areas of the brain known as the "germinal niches," we sought to explore the possibility that DBS influences neural stem cell proliferation locally, as well as more distantly. We studied the brains of a total of 12 idiopathic Parkinson's disease patients that were treated with DBS (the electrode placement occurred 0.5-6 years before death), and who subsequently died of unrelated illnesses. These were compared to the brains of 10 control individuals without CNS disease, and those of 5 PD patients with no DBS. Immunohistochemical analyses of the subventricular zone (SVZ) of the lateral ventricles, the third ventricle lining, and the tissue surrounding the DBS lead revealed significantly greater numbers of proliferating cells expressing markers of the cell cycle, plasticity, and neural precursor cells in PD-DBS tissue compared with both normal brain tissue and tissue from PD patients not treated with DBS. The level of cell proliferation in the SVZ in PD-DBS brains was 2-6 fold greater than that in normal and untreated PD brains. Our data suggest that DBS is capable of increasing cellular plasticity in the brain, and we hypothesize that it may have more widespread effects beyond the electrode location. It is unclear whether these effects of DBS have any symptomatic or other beneficial influences on PD.
    Full-text · Article · Mar 2014 · PLoS ONE
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    • "Regarding patients’ characteristics, our patients had advanced PD but were successfully treated by STN stimulation except for severe FOG. The clinical and motor characteristics of these patients, including young-onset of disease, STN stimulation- and levodopa-responsive akineto-rigid syndrome with STN stimulation and levodopa resistant axial symptoms, is not typical of the natural evolution of PD but reflects the evolution of most PD patients with STN stimulation [39], [40], [41], [42]. They were offered PPNa surgery because under usual dopaminergic treatment, their FOG was not alleviated (contrary to what happens during a levodopa test based on a medication dose exceeding the usual patient’s dosage) and was their main complaint. "
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    ABSTRACT: The pedunculopontine area (PPNa) including the pedunculopontine and cuneiform nuclei, belongs to the mesencephalic locomotor region. Little is known about the oscillatory mechanisms underlying the function of this region in postural and gait control. We examined the modulations of the oscillatory activity of the PPNa and cortex during stepping, a surrogate of gait, and stance in seven Parkinson's disease patients who received bilateral PPNa implantation for disabling freezing of gait (FOG). In the days following the surgery, we recorded behavioural data together with the local field potentials of the PPNa during sitting, standing and stepping-in-place, under two dopaminergic medication conditions (OFF and ON levodopa). Our results showed that OFF levodopa, all subjects had FOG during step-in-place trials, while ON levodopa, stepping was effective (mean duration of FOG decreasing from 61.7±36.1% to 7.3±10.1% of trial duration). ON levodopa, there was an increase in PPNa alpha (5-12 Hz) oscillatory activity and a decrease in beta (13-35 Hz) and gamma (65-90 Hz) bands activity. PPNa activity was not modulated during quiet standing and sitting. Our results confirm the role of the PPNa in the regulation of gait and suggest that, in Parkinson disease, gait difficulties could be related to an imbalance between low and higher frequencies.
    Full-text · Article · Dec 2013 · PLoS ONE
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