Odekerken VJ, van Laar T, Staal MJ, et al. Subthalamic nucleus versus globus pallidus bilateral deep brain stimulation for advanced Parkinson's disease (NSTAPS study): a randomised controlled trial

Department of Neurology, Academic Medical Center, Amsterdam, Netherlands.
The Lancet Neurology (Impact Factor: 21.9). 11/2012; 12(1). DOI: 10.1016/S1474-4422(12)70264-8
Source: PubMed


BACKGROUND: Patients with advanced Parkinson's disease often have rapid swings between mobility and immobility, and many respond unsatisfactorily to adjustments in pharmacological treatment. We assessed whether globus pallidus pars interna (GPi) deep brain stimulation (DBS) gives greater functional improvement than does subthalamic nucleus (STN) DBS. METHODS: We recruited patients from five centres in the Netherlands who were aged 18 years or older, had idiopathic Parkinson's disease, and had, despite optimum pharmacological treatment, at least one of the following symptoms: severe response fluctuations, dyskinesias, painful dystonias, or bradykinesia. By use of a computer-generated randomisation sequence, we randomly assigned patients to receive either GPi DBS or STN DBS (1:1), applying a minimisation procedure according to drug use (levodopa equivalent dose <1000 mg vs ≥1000 mg) and treatment centre. Patients and study assessors (but not those who assessed adverse events) were masked to treatment allocation. We had two primary outcomes: functional health as measured by the weighted Academic Medical Center Linear Disability Scale (ALDS; weighted by time spent in the off phase and on phase) and a composite score for cognitive, mood, and behavioural effects up to 1 year after surgery. Secondary outcomes were symptom scales, activities of daily living scales, a quality-of-life questionnaire, the occurrence of adverse events, and drug use. We used the intention-to-treat principle for all analyses. This trial is registered with www.controlled-trials.com, number ISRCTN85542074. FINDINGS: Between Feb 1, 2007, and March 29, 2011, we enrolled 128 patients, assigning 65 to GPi DBS and 63 to STN DBS. We found no statistically significant difference in either of our primary outcomes: mean change in weighted ALDS (3·0 [SD 14·5] in the GPi group vs 7·7 [23·2] in the STN group; p=0·28) and the number of patients with cognitive, mood, and behavioural side-effects (36 [58%] of 62 patients in the GPi group vs 35 [56%] of 63 patients in the STN group; p=0·94). Secondary outcomes showed larger improvements in off-drug phase in the STN group compared with the GPi group in the mean change in unified Parkinson's disease rating scale motor examination scores (20·3 [16·3] vs 11·4 [16·1]; p=0·03), the mean change in ALDS scores (20·3 [27·1] vs 11·8 [18·9]; p=0·04), and medication (mean levodopa equivalent drug reduction: 546 [SD 561] vs 208 [521]; p=0·01). We recorded no difference in the occurrence of adverse events between the two groups. Other secondary endpoints showed no difference between the groups. INTERPRETATION: Although there was no difference in our primary outcomes, our findings suggest that STN could be the preferred target for DBS in patients with advanced Parkinson's disease. FUNDING: Stichting Internationaal Parkinson Fonds, Prinses Beatrix Fonds, and Parkinson Vereniging.

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    • "Despite differences in definitions between individual research groups, the occurrence of cognitive/psychiatric side is consistently reported (Benabid et al. 2009). Case studies describe rare neuropsychiatric side effects including apathy , compulsive behavior, hypersexuality, cognitive dysfunction as well as clinical depression including suicide (Temel et al. 2005), and a recent, larger study reports emotional lability in patients receiving DBS in the STN as well as in the internal segment of the globus pallidus (GPi) (Odekerken et al. 2013). We would like to note that a direct association between DBS surgery and an increased risk for suicide ideation and behavior has not been shown (Weintraub et al. 2013). "
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    ABSTRACT: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is used to relieve motor symptoms of Parkinson's disease. A tripartite system of STN subdivisions serving motoric, associative, and limbic functions was proposed, mainly based on tracing studies, which are limited by low numbers of observations. The evidence is compelling and raises the question as to what extent these functional zones are anatomically segregated. The majority of studies indicate that there is anatomical overlap between STN functional zones. Using ultrahigh-resolution magnetic resonance imaging techniques it is now possible to visualize the STN with high spatial resolution, and it is feasible that in the near future stereotactic guided placement of electrical stimulators aided by high-resolution imaging will allow for more specific stimulation of the STN. The neuroanatomical and functional makeup of these subdivisions and their level of overlap would benefit from clarification before serving as surgical targets. We discuss histological and imaging studies, as well as clinical observations and electrophysiological recordings in DBS patients. These studies provide evidence for a topographical organization within the STN, although it remains unclear to what extent functionally and anatomically distinct subdivisions overlap.
    Brain Structure and Function 04/2015; 220(6). DOI:10.1007/s00429-015-1047-2 · 5.62 Impact Factor
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    • "The STN is one of the preferred targets in deep brain stimulation (DBS) treatment of PD patients, with greater clinical benefits than those obtained by stimulating other sites [Krack et al., 2000; Odekerken et al., 2013; Volkmann et al., 2004]. However, despite the significant experience accumulated on DBS in the past years, the mechanisms by which this surgical therapy improves parkinsonian symptoms are not yet fully elucidated [Chiken and Nambu, 2014]. "
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    ABSTRACT: Abstract: Neurophysiological changes within the cortico-basal ganglia-thalamocortical circuits appear to be a characteristic of Parkinson’s disease (PD) pathophysiology. The subthalamic nucleus (STN) is one of the basal ganglia components showing pathological neural activity patterns in PD. In this study, perfusion imaging data, acquired noninvasively using arterial spin-labeled (ASL) perfusion MRI, were used to assess the resting state functional connectivity (FC) of the STN in 24 early-to-moderate PD patients and 34 age-matched healthy controls, to determine whether altered FC in the very low frequency range of the perfusion time signal occurs as a result of the disease. Our results showed that the healthy STN was functionally connected with other nuclei of the basal ganglia and the thalamus, as well as with discrete cortical areas including the insular cortex and the hippocampus. In PD patients, connectivity of the STN was increased with two cortical areas involved in motor and cognitive processes. These findings suggest that hyperconnectivity of the STN could underlie some of the motor and cognitive deficits often present even at early stages of the disease. The FC measures provided good discrimination between controls and patients, suggesting that ASL-derived FC metrics could be a putative PD biomarker.
    Human Brain Mapping 04/2015; DOI:10.1002/hbm.22747 · 5.97 Impact Factor
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    • "While several brain regions can be targeted with DBS, the subthalamic nucleus (STN) has proven to be highly effective [4] [5]. In fact, numerous studies have demonstrated the efficacy of STN DBS in reducing PD-related motor symptoms as well as reducing the motor complications associated with drug treatment [4] [5] [6] [7] [8] [9]. Concomitantly, others have demonstrated that STN DBS may also lead to improved QoL [10]. "
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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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