Article

Long-term outcomes of bilateral subthalamic nucleus stimulation in patients with advanced Parkinson's disease.

The Parkinson's Institute, Sunnyvale, CA, USA.
Stereotactic and Functional Neurosurgery (Impact Factor: 1.48). 01/2006; 84(5-6):221-7.
Source: PubMed

ABSTRACT In patients with advanced Parkinson's disease (PD), deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been shown to improve motor function and decrease medication requirements in the short term. However, the long-term benefits of DBS are not yet established.
It was the aim of this study to evaluate long-term outcomes of patients with PD treated with bilateral DBS of the STN.
Thirty-three subjects who had bilateral STN DBS were followed prospectively after surgery. We evaluated subjects, using the Unified Parkinson's Disease Rating Scale (UPDRS), preoperatively, 12 months after surgery and at a long-term follow-up visit. Ratings were performed on and off dopaminergic medications. We compared postoperative UPDRS scores, dyskinesia ratings and medication dosages with preoperative values.
Twenty-seven subjects had evaluations beyond 18 months (median 33.7 months). Total UPDRS scores in the 'medication-off' state were improved by 37% (p < 0.001) at 12 months and 17.7% (p = 0.0051) at the long-term evaluation. Medication-off state UPDRS part III scores were significantly improved at both 1 year and at the last evaluation (37.6 and 29.3%; p < 0.001). Dopaminergic medication requirements were decreased by 35.3% (p < 0.001) during the first postoperative year and remained below preoperative levels at the long-term evaluation. Average duration of 'off' time remained decreased by about 40% at both 1 year and at the time of last evaluation. Subjects had a sustained reduction in dyskinesia severity (88.6% at 1 year and 68.8% at last evaluation).
In this cohort of subjects with advanced PD, bilateral STN stimulation improved 'off' medication motor function, reduced time spent in the medication-off state and reduced medication requirements for up to 4 years after surgery. We conclude that STN DBS is an effective long-term therapy for selected patients with advanced PD.

1 Bookmark
 · 
101 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Efficacy of deep brain stimulation (DBS) for motor signs of Parkinson's disease (PD) depends in part on post-operative programming of stimulus parameters. There is a need for a systematic approach to tuning parameters based on patient physiology. We used a physiologically realistic computational model of the basal ganglia network to investigate the emergence of a 34 Hz oscillation in the PD state and its optimal suppression with DBS. Discrete time transfer functions were fit to post-stimulus time histograms (PSTHs) collected in open-loop, by simulating the pharmacological block of synaptic connections, to describe the behavior of the basal ganglia nuclei. These functions were then connected to create a mean-field model of the closed-loop system, which was analyzed to determine the origin of the emergent 34 Hz pathological oscillation. This analysis determined that the oscillation could emerge from the coupling between the globus pallidus external (GPe) and subthalamic nucleus (STN). When coupled, the two resonate with each other in the PD state but not in the healthy state. By characterizing how this oscillation is affected by subthreshold DBS pulses, we hypothesize that it is possible to predict stimulus frequencies capable of suppressing this oscillation. To characterize the response to the stimulus, we developed a new method for estimating phase response curves (PRCs) from population data. Using the population PRC we were able to predict frequencies that enhance and suppress the 34 Hz pathological oscillation. This provides a systematic approach to tuning DBS frequencies and could enable closed-loop tuning of stimulation parameters.
    Journal of Computational Neuroscience 08/2014; 37(3). · 2.09 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: There is a need to explore non-dopaminergic approaches to treating balance and gait problems in PD. There is emerging evidence on the role of cholinergic denervation of the PPN-thalamus system and falls in PD. Preliminary clinical trial data suggest that the subgroup of PD patients with frequent falls may be suitable candidates for future cholinergic augmentation clinical trials. Recent controlled clinical trials using methylphenidate have been unable to confirm earlier reports of improved gait in PD. Although progressive deterioration of axial motor symptoms occur with DBS of the STN or GPi, new preliminary research suggests that other surgical stimulation sites, such as the PPN, may have a potential benefit on gait and balance impairments in PD. Ongoing vigorous exercise and physical fitness should be highly encouraged to patients with PD who are at risk of physical deconditioning and fear of falling but effective anti-fall physical therapy interventions remain an unmet clinical need.
    US neurology. 11/2011; 7(2):100-108.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Gait dysfunction is common in advancing Parkinson's disease and has a disappointing response to dopamine replacement and subthalamic nucleus deep brain stimulation programming parameters. Low-frequency stimulation, less than 130 Hz in combination with increased voltage, has been shown to decrease freezing episodes and number of steps with little impact on overall performance measured by the Unified Parkinson's Disease Rating Scale. This was in the setting of delivering the same total energy, which required both a change in voltage and frequency. We wanted to determine if the benefit came from low frequency alone. We enrolled 20 Parkinson's patients who were at least three months in postbilateral subthalamic deep brain stimulation and reported gait changes. Subjects held their Parkinson's medications overnight, and following a baseline evaluation, they were randomly assigned to both 60 and 130 Hz stimulation in a blinded fashion with all other parameters held constant. Each subject was set at each frequency twice during the study, with a 60-min stimulation interval prior to each gait evaluation. There was no significant difference between the two frequencies, with the primary outcome measure of stride length. Two of the 20 patients reported a significant subjective improvement in their gait with no statistical difference in their outcomes. There also was less tremor control at 60 Hz. We were unable to demonstrate improved gait with lower frequency stimulation as suggested by prior studies. This may have been because of the decreased energy delivered from the lower frequency and unchanged voltage.
    Neuromodulation 10/2013; · 1.79 Impact Factor