Attenuation of fluctuating striatal synaptic dopamine levels in patients with Parkinson disease in response to subthalamic nucleus stimulation: a positron emission tomography study

2005 ◽  
Vol 103 (6) ◽  
pp. 968-973 ◽  
Author(s):  
Taro Nimura ◽  
Keiichiro Yamaguchi ◽  
Tadashi Ando ◽  
Satoshi Shibuya ◽  
Takanori Oikawa ◽  
...  

Object. The “wearing-off” phenomenon often hampers the treatment of Parkinson disease (PD). Although deep brain stimulation (DBS) of the subthalamic nucleus (STN) is known to ameliorate the wearing-off phenomenon, the mechanism by which it does this remains unclear. As part of an inquiry into the mechanism of STN DBS, the authors measured synaptic dopamine levels in the striatum by performing positron emission tomography (PET) with [11C]raclopride. Methods. Three patients with PD who were experiencing the wearing-off phenomenon underwent PET scanning before and after DBS of the STN. The clinical features in these patients were evaluated by applying the Hoehn and Yahr, United Parkinson's Disease Rating, and Schwab and England Activities of Daily Living Scales. Before and after surgery, PET scans were obtained using [11C]raclopride prior to and 1 hour following an oral administration of levodopa. Regions of interest for the [11C]raclopride binding potential (RacloBP) were set in the bilateral putamen and the caudate nucleus. All clinical scores were dramatically improved postoperatively. Deep brain stimulation of the STN reduced the baseline RacloBP in both the putamen and caudate nucleus, but the differences between the pre- and postoperative levels were insignificant. Before DBS of the STN, the levodopa administration significantly reduced RacloBP in the putamen (p < 0.0001). Postoperatively the drug-induced reduction in RacloBP became statistically insignificant. The drug-induced increase in synaptic dopamine concentrations in the putamen preoperatively was estimated to be approximately four times higher than that after surgery (p < 0.01). The drug-induced RacloBP change in the caudate nucleus was similar to that in the putamen, although the magnitude of the change was lower (p < 0.005). The drug-induced increase in the caudate nucleus was also reduced postoperatively (p < 0.05). Conclusions. Deep brain stimulation of the STN induces the stabilization of synaptic dopamine concentrations in the striatum and may attribute to the alleviation of levodopa-related motor fluctuations.

2002 ◽  
Vol 96 (4) ◽  
pp. 666-672 ◽  
Author(s):  
Tanya Simuni ◽  
Jurg L. Jaggi ◽  
Heather Mulholland ◽  
Howard I. Hurtig ◽  
Amy Colcher ◽  
...  

Object. Palliative neurosurgery has reemerged as a valid therapy for patients with advanced Parkinson disease (PD) that is complicated by severe motor fluctuations. Despite great enthusiasm for long-term deep brain stimulation (DBS) of the subthalamic nucleus (STN), existing reports on this treatment are limited. The present study was designed to investigate the safety and efficacy of bilateral stimulation of the STN for the treatment of PD. Methods. In 12 patients with severe PD, electrodes were stereotactically implanted into the STN with the assistance of electrophysiological conformation of the target location. All patients were evaluated preoperatively during both medication-off and -on conditions, as well as postoperatively at 3, 6, and 12 months during medication-on and -off states and stimulation-on and -off conditions. Tests included assessments based on the Unified Parkinson's Disease Rating Scale (UPDRS) and timed motor tests. The stimulation effect was significant in patients who were in the medication-off state, resulting in a 47% improvement in the UPDRS Part III (Motor Examination) score at 12 months, compared with preoperative status. The benefit was stable for the duration of the follow-up period. Stimulation produced no additional benefit during the medication-on state, however, when compared with patient preoperative status. Significant improvements were made in reducing dyskinesias, fluctuations, and duration of off periods. Conclusions. This study demonstrates that DBS of the STN is an effective treatment for patients with advanced, medication-refractory PD. Deep brain stimulation of the STN produced robust improvements in motor performance in these severely disabled patients while they were in the medication-off state. Serious adverse events were common in this cohort; however, only two patients suffered permanent sequelae.


2005 ◽  
Vol 103 (6) ◽  
pp. 956-967 ◽  
Author(s):  
Frances Weaver ◽  
Kenneth Follett ◽  
Kwan Hur ◽  
Dolores Ippolito ◽  
Matthew Stern

Object. Deep brain stimulation (DBS) to treat advanced Parkinson disease (PD) has been focused on one of two anatomical targets: the subthalamic nucleus (STN) and the globus pallidus internus (GPI). Authors of more than 65 articles have reported on bilateral DBS outcomes. With one exception, these studies involved pre- and postintervention comparisons of a single target. Despite the paucity of data directly comparing STN and GPI DBS, many clinicians already consider the STN to be the preferred target site. In this study the authors conducted a metaanalysis of the existing literature on patient outcomes following DBS of the STN and the GPI. Methods. This metaanalysis includes 31 STN and 14 GPI studies. Motor function improved significantly following stimulation (54% in patients whose STN was targeted and 40% in those whose GPI was stimulated), with effect sizes (ESs) of 2.59 and 2.04, respectively. After controlling for participant and study characteristics, patients who had undergone either STN or GPI DBS experienced comparable improved motor function following surgery (p = 0.094). The performance of activities of daily living improved significantly in patients with either target (40%). Medication requirements were significantly reduced following stimulation of the STN (ES = 1.51) but did not change when the GPI was stimulated (ES = −0.02). Conclusions. In this analysis the authors highlight the need for uniform, detailed reporting of comprehensive motor and nonmotor DBS outcomes at multiple time points and for a randomized trial of bilateral STN and GPI DBS.


2005 ◽  
Vol 102 (1) ◽  
pp. 53-59 ◽  
Author(s):  
Hans-Holger Capelle ◽  
Richard K. Simpson ◽  
Martin Kronenbuerger ◽  
Jochen Michaelsen ◽  
Volker Tronnier ◽  
...  

Object. Deep brain stimulation (DBS) has become an accepted therapy for movement disorders such as Parkinson disease (PD) and essential tremor (ET), when these conditions are refractory to medical treatment. The presence of a cardiac pacemaker is still considered a contraindication for DBS in functional neurosurgery. The goal of this study was to evaluate the technical and clinical management of DBS for the treatment of movement disorders in elderly patients with cardiac pacemakers. Methods. Six patients with cardiac pacemakers underwent clinical and cardiac examinations to analyze the safety of DBS in the treatment of movement disorders. Four patients suffered from advanced PD and two patients had ET. The mean age of these patients at surgery was 69.5 years (range 63–79 years). The settings of the pacemakers were programmed in a manner considered to minimize the chance of interference between the two systems. There were no adverse events during surgery. Four patients underwent stimulation of the thalamic ventralis intermedius nucleus (VIM), and two patients stimulation of the subthalamic nucleus. In general, bipolar sensing was chosen for the cardiac pacemakers. In all but one patient the quadripolar DBS electrodes were programmed for bipolar stimulation. Several control electrocardiography studies, including 24-hour monitoring, did not show any interference between the two systems. At the time this paper was written the patients had been followed up for a mean of 25.3 months (range 4–48 months). Conclusions. In certain conditions it is safe for patients with cardiac pacemakers to receive DBS for treatment of concomitant movement disorders. Cardiac pacemakers should not be viewed as a general contraindication for DBS in patients with movement disorders.


2005 ◽  
Vol 103 (2) ◽  
pp. 246-251 ◽  
Author(s):  
Valerie Voon ◽  
Jean Saint-Cyr ◽  
Andres M. Lozano ◽  
Elena Moro ◽  
Yu Yan Poon ◽  
...  

Object. Postoperative psychiatric symptoms have been associated with subthalamic deep brain stimulation (DBS) for Parkinson disease (PD), and preoperative psychiatric vulnerability, the effects of surgery, stimulation, medication changes, and psychosocial adjustment have been proposed as causative factors. The variables involved in whether preoperative psychiatric symptoms improve or worsen following surgery are not yet known. In the present study, preoperative psychiatric symptoms were systematically assessed in patients with PD presenting for routine preoperative psychiatric assessment. Methods. Forty consecutive patients with PD presenting for DBS were interviewed using the Mini International Neuropsychiatric Inventory. Current depressive symptoms were quantified using clinician- and patient-rated depression scales. Seventy-eight percent of patients had at least one lifetime or current Axis I psychiatric diagnosis. The prevalence of depression was 60% (95% confidence interval [CI] 45–85), psychosis 35% (95% CI 25–50), and anxiety 40% (95% CI 25–55). These prevalence rates were comparable to or greater than those in the general population of patients with PD. Twenty-three percent of patients required psychiatric treatment for current symptoms prior to being considered eligible for DBS. Conclusions. As part of the selection process for surgery, members of the study population were chosen for their lack of overt dementia or other active disabling psychiatric symptomatology. The incidence rates of psychiatric disorders, including those diseases occurring in the general population affected with PD, were greater than expected. Data in the present study lead one to question the reliability of patient-rated depression scales as the sole instrument for assessing depression. The authors highlight the need for evidence-based guidelines in the management of these preoperative symptoms as well as the involvement of psychiatric personnel in the assessment and management of these symptoms.


2000 ◽  
Vol 93 (5) ◽  
pp. 784-790 ◽  
Author(s):  
Nathalie Vayssiere ◽  
Simone Hemm ◽  
Michel Zanca ◽  
Marie Christine Picot ◽  
Alain Bonafe ◽  
...  

Object. The actual distortion present in a given series of magnetic resonance (MR) images is difficult to establish. The purpose of this study was to validate an MR imaging—based methodology for stereotactic targeting of the internal globus pallidus during electrode implantation in children in whom general anesthesia had been induced.Methods. Twelve children (mean follow up 1 year) suffering from generalized dystonia were treated with deep brain stimulation by using a head frame and MR imaging. To analyze the influence of distortions at every step of the procedure, the geometrical characteristics of the frame were first controlled using the localizer as a phantom. Then pre- and postoperative coordinates of fixed anatomical landmarks and electrode positions, both determined with the head frame in place, were statistically compared.No significant difference was observed between theoretical and measured dimensions of the localizer (Student's t-test, |t| > 2.2 for 12 patients) in the x, y, and z directions.No significant differences were observed (Wilcoxon paired-sample test) between the following: 1) pre- and postoperative coordinates of the anterior commissure (AC) (Δx = 0.3 ± 0.29 mm and Δy = 0.34 ± 0.32 mm) and posterior commissure (PC) (Δx = 0.15 ± 0.18 mm and Δy = 0.34 ± 0.25 mm); 2) pre- and postoperative AC—PC distance (ΔL = 0.33 ± 0.22 mm); and 3) preoperative target and final electrode position coordinates (Δx = 0.24 ± 0.22 mm; Δy = 0.19 ± 0.16 mm).Conclusions. In the authors' center, MR imaging distortions did not induce detectable errors during stereotactic surgery in dystonic children. Target localization and electrode implantation could be achieved using MR imaging alone after induction of general anesthesia. The remarkable postoperative improvement in these patients confirmed the accuracy of the procedure (Burke—Marsden—Fahn Dystonia Rating Scale score Δ = −83.8%).


2002 ◽  
Vol 97 (2) ◽  
pp. 461-466 ◽  
Author(s):  
Dipankar Nandi ◽  
Simon Parkin ◽  
Richard Scott ◽  
Jonathan L. Winter ◽  
Carole Joint ◽  
...  

✓ The authors report the neurological, neurophysiological, and neuropsychological effects of using long-term bilateral pallidal high-frequency deep brain stimulation (DBS) in a case of disabling camptocormia. Deep brain stimulation electrodes were implanted stereotactically to target the globus pallidus internus (GPi) bilaterally. Local field potentials (FPs) were recorded using the DBS electrodes and concurrent abdominal flexor electromyography (EMG) potentials during camptocormic episodes. Videotaped assessments of the movement disorder and neuropsychological evaluations of the patient before implantation and 6 months after initiation of pallidal stimulation were recorded. There was significant functional improvement following long-term pallidal stimulation, and some improvement was noted in neuropsychological scores. A temporal correlation between the GPi FPs and EMG-recorded rectus abdominis potentials was evident. There were no treatment-related adverse effects. The authors have found that long-term pallidal stimulation was safe and offered functional benefit to a patient with this severely disabling condition. The physiological studies may help further the understanding of the pathophysiology of this rare entity.


2005 ◽  
Vol 102 (6) ◽  
pp. 1137-1141 ◽  
Author(s):  
Naoki Nakano ◽  
Takuya Uchiyama ◽  
Takeshi Okuda ◽  
Masahiko Kitano ◽  
Mamoru Taneda

✓ The authors report a case of hemichorea—hemiballism (HC-HB) that was successfully treated using deep brain stimulation (DBS). A 65-year-old right-handed man exhibited a sudden onset of right HC-HB without a diabetic coma. At admission T1-weighted magnetic resonance (MR) images revealed a high-intensity signal in the left striatum, contralateral to the patient's involuntary movements. The HC-HB continued for 5 months after onset of the condition despite medical treatment and a decreased intensity of the signal on T1-weighted MR images. The patient underwent placement of a quadripolar DBS electrode in the left thalamus, including the left ventral oralis (VO) anterior and posterior nuclei (the VO complex). Postoperatively, the right-sided HC-HB disappeared rapidly during electrical stimulation and there were no neurological deficits. The authors demonstrate that DBS can be an effective treatment for medically refractory HC-HB. This is the first case of HC-HB that has been successfully treated with DBS.


2003 ◽  
Vol 99 (3) ◽  
pp. 489-495 ◽  
Author(s):  
Galit Kleiner-Fisman ◽  
David N. Fisman ◽  
Elspeth Sime ◽  
Jean A. Saint-Cyr ◽  
Andres M. Lozano ◽  
...  

Object. The use of deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been associated with a marked initial improvement in individuals with advanced Parkinson disease (PD). Few data are available on the long-term outcomes of this procedure, however, or whether the initial benefits are sustained over time. The authors present the long-term results of a cohort of 25 individuals who underwent bilateral DBS of the STN between 1996 and 2001 and were followed up for 1 year or longer after implantation of the stimulator. Methods. Patients were evaluated at baseline and repeatedly after surgery by using the Unified Parkinson's Disease Rating Scale (UPDRS); the scale was applied to patients during periods in which antiparkinsonian medications were effective and periods when their effects had worn off. Postoperative UPDRS total scores and subscores, dyskinesia scores, and drug dosages were compared with baseline values, and changes in the patients' postoperative scores were evaluated to assess the possibility that the effect of DBS diminished over time. In this cohort the median duration of follow-up review was 24 months (range 12–52 months). The combined (ADL and motor) total UPDRS score during the medication-off period improved after 1 year, decreasing by 42% relative to baseline (95% confidence interval [CI 35–50%], p < 0.001) and the motor score decreased by 48% (95% CI 42–55%, p < 0.001). These gains did diminish over time, although a sustained clinical benefit remained at the time of the last evaluation (41% improvement over baseline, 95% CI 31–50%; p < 0.001). Axial subscores at the time of the last evaluation showed only a trend toward improvement (p = 0.08), in contrast to scores for total tremor (p < 0.001), rigidity (p < 0.001), and bradykinesia (p = 0.003), for which highly significant differences from baseline were still present at the time of the last evaluation. Medication requirements diminished substantially, with total medication doses reduced by 38% (95% CI 27–48%, p < 0.001) at 1 year and 36% (95% CI 25–48%, p < 0.001) at the time of the last evaluation; this decrease may have accounted, at least in part, for the significant decrease of 46.4% (95% CI 20.2–72.5%, p = 0.007) in dyskinesia scores obtained by patients during the medication-on period. No preoperative demographic variable, such as the patient's age at the time of disease onset, age at surgery, sex, duration of disease before surgery, preoperative drug dosage, or preoperative severity of dyskinesia, was predictive of long-term outcome. The only predictor of a better outcome was the patient's preoperative response to levodopa. Conclusions. In this group of patients with advanced PD who underwent bilateral DBS of the STN, sustained improvement in motor function was present a mean of 2 years after the procedure, and sustained reductions in drug requirements were also achieved. Improvements in tremor, rigidity, and bradykinesia were more marked and better sustained over time than improvements in axial symptoms. A good preoperative response to levodopa predicted a good response to surgery.


1996 ◽  
Vol 85 (6) ◽  
pp. 1181-1183 ◽  
Author(s):  
Jacques Favre ◽  
Jamal M. Taha ◽  
Timothy Steel ◽  
Kim J. Burchiel

✓ The authors report a new technique to anchor deep brain stimulation electrodes using a titanium microplate. This technique has been safely used to secure 20 quadripolar deep brain stimulation electrodes implanted for movement disorders (18 electrodes) and pain (two electrodes). Twelve electrodes were implanted in the thalamus, four in the subthalamic nucleus, and four in the pallidum. No electrode migration or rupture occurred, and all electrodes have been shown to work properly after internalization of the system.


2002 ◽  
Vol 96 (3) ◽  
pp. 615-618 ◽  
Author(s):  
Caglar Berk ◽  
Christopher R. Honey

✓ Isolated head tremor is rare, but can be disabling. The authors' experience with the treatment of limb tremor due to essential tremor led them to consider using bilateral thalamic deep brain stimulation (DBS) in two patients presenting only with disabling head tremor. One patient exhibited no peripheral tremor and the other displayed only a slight upper-limb tremor. Both patients underwent placement of units that apply simultaneous bilateral thalamic DBS. Surgical targets were verified by using intraoperative macrostimulation, and the stimulators were implanted during the same surgery. Patients were videotaped preoperatively and at 2, 4, 6, and 9 months postoperatively during periods in which the stimulators were turned on and off. Videotapes were randomized and rated for resting, postural, and action tremors according to the Fahn clinical rating scale for tremor. Because this scale is not designed for head tremor, the patients were also evaluated on the basis of a functional scale that reflected their quality of life and the amount of disability caused by head tremor. Both patients experienced no tremor after their stimulators were turned on and properly adjusted at the 6th postoperative week. The patients were followed for a total of 9 months and results remained stable throughout this period. No complications were encountered. Bilateral thalamic DBS appears to be an effective and safe treatment for isolated head tremor in patients with essential tremor. The authors present a scale for the functional assessment of head tremor.


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