Okun, M. S. et al. Subthalamic deep brain stimulation with a constant-current device in Parkinson's disease: an open-label randomised controlled trial. Lancet Neurol. 11, 140-149

Department of Neurology, Center for Movement Disorders and Neurorestoration, University of Florida College of Medicine, Gainesville, FL 32607, USA. .edu
The Lancet Neurology (Impact Factor: 21.9). 02/2012; 11(2):140-9. DOI: 10.1016/S1474-4422(11)70308-8
Source: PubMed

ABSTRACT The effects of constant-current deep brain stimulation (DBS) have not been studied in controlled trials in patients with Parkinson's disease. We aimed to assess the safety and efficacy of bilateral constant-current DBS of the subthalamic nucleus.
This prospective, randomised, multicentre controlled trial was done between Sept 26, 2005, and Aug 13, 2010, at 15 clinical sites specialising in movement disorders in the USA. Patients were eligible if they were aged 18-80 years, had Parkinson's disease for 5 years or more, and had either 6 h or more daily off time reported in a patient diary of moderate to severe dyskinesia during waking hours. The patients received bilateral implantation in the subthalamic nucleus of a constant-current DBS device. After implantation, computer-generated randomisation was done with a block size of four, and patients were randomly assigned to the stimulation or control group (stimulation:control ratio 3:1). The control group received implantation without activation for 3 months. No blinding occurred during this study, and both patients and investigators were aware of the treatment group. The primary outcome variable was the change in on time without bothersome dyskinesia (ie, good quality on time) at 3 months as recorded in patients' diaries. Patients were followed up for 1 year. This trial is registered with, number NCT00552474.
Of 168 patients assessed for eligibility, 136 had implantation of the constant-current device and were randomly assigned to receive immediate (101 patients) or delayed (35 patients) stimulation. Both study groups reported a mean increase of good quality on time after 3 months, and the increase was greater in the stimulation group (4·27 h vs 1·77 h, difference 2·51 [95% CI 0·87-4·16]; p=0·003). Unified Parkinson's disease rating scale motor scores in the off-medication, on-stimulation condition improved by 39% from baseline (24·8 vs 40·8). Some serious adverse events occurred after DBS implantation, including infections in five (4%) of 136 patients and intracranial haemorrhage in four (3%) patients. Stimulation of the subthalamic nucleus was associated with dysarthria, fatigue, paraesthesias, and oedema, whereas gait problems, disequilibrium, dyskinesia, and falls were reported in both groups.
Constant-current DBS of the subthalamic nucleus produced significant improvements in good quality on time when compared with a control group without stimulation. Future trials should compare the effects of constant-current DBS with those of voltage-controlled stimulation.
St Jude Medical Neuromodulation Division.

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Available from: Michele Tagliati, Sep 28, 2015
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    • "Stimulation devices of the first generation delivered electrical stimulation in a voltage-controlled mode whereas following devices predominantly use the constant-current mode or can be switched into this mode. In comparison to constant-current devices, where the stimulation field is kept stable in size, the stimulation field produced by constant-voltage devices is vulnerable to changing tissue impedances (Lempka et al., 2010; Okun et al., 2012). The most frequent programming parameters are monopolar stimulation, impulse duration 60–90 µs and frequency 130 Hz (Volkmann et al., 2006). "
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    ABSTRACT: Deep brain stimulation has become a well-established symptomatic treatment for Parkinson's disease during the last 25 years. Besides improving motor symptoms and long-term motor complications, positive effects on patients' mobility, activities of daily living, emotional well-being and health-related quality of life have been recognized. Apart from that, numerous clinical trials analyzed effects on non-motor symptoms and side effects of deep brain stimulation. Several technical issues and stimulation paradigms have been and are still being developed to optimize the therapeutic effects, minimize the side effects and facilitate handling. This review summarizes current therapeutic issues, i.e., patient and target selection, surgical procedure and programming paradigms. In addition it focuses on neuropsychological effects and side effects of deep brain stimulation.
    Neural Regeneration Research 07/2015; 10(7). DOI:10.4103/1673-5374.160094 · 0.22 Impact Factor
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    • "It should be noted, however, that clinically available anti-cholinergics (e.g., trihexyphenidyl, benztropine, etc.) mainly act as competitive antagonists at mAChRs. A stepwise executive dysfunction has been described in cognitively intact PD patients (Taylor et al., 1986) who suffer damage to the frontal lobes and/or fibers connecting the frontal lobes with the head of the caudate during electrode implantation for deep brain stimulation (Okun et al., 2012). The role of [ 123 I]5IA- SPECT as a screening tool for identifying patients at risk for (surgery-related) cognitive decline should be further investigated. "
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    ABSTRACT: We investigated in vivo brain nicotinic acetylcholine receptor (nAChR) distribution in cognitively intact subjects with Parkinson's disease (PD) at an early stage of the disease. Fourteen patients and 13 healthy subjects were imaged with single photon emission computed tomography and the radiotracer 5-[(123)I]iodo-3-[2(S)-2-azetidinylmethoxy]pyridine ([(123)I]5IA). Patients were selected according to several criteria, including short duration of motor signs (<7 years) and normal scores at an extensive neuropsychological evaluation. In PD patients, nAChR density was significantly higher in the putamen, the insular cortex and the supplementary motor area and lower in the caudate nucleus, the orbitofrontal cortex, and the middle temporal gyrus. Disease duration positively correlated with nAChR density in the putamen ipsilateral (ρ = 0.56, p < 0.05) but not contralateral (ρ = 0.49, p = 0.07) to the clinically most affected hemibody. We observed, for the first time in vivo, higher nAChR density in brain regions of the motor and limbic basal ganglia circuits of subjects with PD. Our findings support the notion of an up-regulated cholinergic activity at the striatal and possibly cortical level in cognitively intact PD patients at an early stage of disease.
    Frontiers in Aging Neuroscience 08/2014; 6:213. DOI:10.3389/fnagi.2014.00213 · 4.00 Impact Factor
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    • "There is no cure for the disease and the medical and increasingly used surgical treatments aim at alleviating the symptoms. Over the last decade, deep brain stimulation (DBS) of different brain targets, mainly DBS of the subthalamic nucleus (STN), has become an established surgical procedure for patients with advanced PD [2,3]. According to estimates, to date more than 100 000 patients worldwide have had DBS [4]. "
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    ABSTRACT: Deep brain stimulation (DBS) is an established treatment for patients with advanced parkinson's disease (PD). Research shows that women are under-represented among patients undergoing DBS surgery. This may be due to gender-biased selection of patients, but patients' wishes and attitudes may also contribute. This study investigated the decision making process to undergo DBS from the patient's perspective, and explored any gender patterns in the participants' decision-making. All patients operated on with DBS for PD at the University Hospital of Northern Sweden between January 2002 and April 2010 were invited to an interview study. In this way 39 patients were recruited, 31 men and eight women. Three additional women, operated elsewhere, were recruited to acheive a more gender-balanced sample. In a mixed-method analysis, the interviews were analysed according to the constant comparison technique in grounded theory and descriptive statistics was used to present demographics and compare categories. Three different approaches to DBS were identified among the patients. 'Taking own initiative', included 48% of the patients and implied that the patients' own initiatives and arguments had been crucial for having surgery. 'Agreeing when offered', and accepting DBS when suggested by doctors embraced 43%. The third approach, 'Hesitating and waiting' included < 10% of the patients. Most of the men were either 'taking own initiative' or 'agreeing when offered'. The 11 women were evenly distributed in all three approaches. Among the interviewed, more women than men expressed strong fear of complications and more women consulted friends and relatives prior to deciding about DBS. Half of the patients had held a leadership position at work or in another organisation, and among patients 'taking own initiative' the proportion with leadership experiences was 80%. At time for surgery ten men but no woman were professionally active. This study suggests that many patients with advanced PD have to argue and struggle with their clinicians in order to be referred to a DBS-team. The study further suggests that patients' wishes, behaviour and position in society may all contribute to the skewed gender distribution among patients treated with DBS.
    BMC Neurology 04/2014; 14(1):89. DOI:10.1186/1471-2377-14-89 · 2.04 Impact Factor
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