Increased anteroventral striatal dopamine transporter and motor recovery after subthalamic deep brain stimulation in Parkinson’s disease

2021 ◽  
pp. 1-11
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Dopamine Transporter ◽  
Motor Recovery ◽  
Striatal Dopamine ◽  
Percentage Increase ◽  
Percentage Reduction ◽  
Stn Dbs ◽  
Deep Brain

OBJECTIVE Subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease is effective; however, its mechanism is unclear. To investigate the degree of neuronal terminal survival after STN-DBS, the authors examined the striatal dopamine transporter levels before and after treatment in association with clinical improvement using PET with [11C]2β-carbomethoxy-3β-(4-fluorophenyl)tropane ([11C]CFT). METHODS Ten patients with Parkinson’s disease who had undergone bilateral STN-DBS were scanned twice with [11C]CFT PET just before and 1 year after surgery. Correlation analysis was conducted between [11C]CFT binding and off-period Unified Parkinson’s Disease Rating Scale (UPDRS) scores assessed preoperatively and postoperatively. RESULTS [11C]CFT uptake reduced significantly in the posterodorsal putamen contralateral to the parkinsonism-dominant side after 1 year; however, an increase was noted in the contralateral anteroventral putamen and ipsilateral ventral caudate postoperatively (p < 0.05). The percentage increase in [11C]CFT binding was inversely correlated with the preoperative binding level in the bilateral anteroventral putamen, ipsilateral ventral caudate, contralateral anterodorsal putamen, contralateral posteroventral putamen, and contralateral nucleus accumbens. The percentage reduction in UPDRS-II score was significantly correlated with the percentage increase in [11C]CFT binding in the ipsilateral anteroventral putamen (p < 0.05). The percentage reduction in UPDRS-III score was significantly correlated with the percentage increase in [11C]CFT binding in the ipsilateral anteroventral putamen, ventral caudate, and nucleus accumbens (p < 0.05). CONCLUSIONS STN-DBS increases dopamine transporter levels in the anteroventral striatum, which is correlated with the motor recovery and possibly suggests the neuromodulatory effect of STN-DBS on dopaminergic terminals in Parkinson’s disease patients. A preoperative level of anterior striatal dopamine transporter may predict reserve capacity of STN-DBS on motor recovery.

Striatal dopamine transporter availability and individual clinical course within the 1-year follow-up of deep brain stimulation of the subthalamic nucleus in patients with Parkinson’s disease

2021 ◽  
pp. 1-7
Author(s):  
Julia Löser ◽  
Julia Luthardt ◽  
Michael Rullmann ◽  
David Weise ◽  
Osama Sabri ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Clinical Outcome ◽  
Dopamine Transporter ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Striatal Dopamine ◽  
Stn Dbs ◽  
Deep Brain

OBJECTIVEDegeneration of dopaminergic neurons in the substantia nigra projecting to the striatum is responsible for the motor symptoms in Parkinson’s disease (PD). Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established procedure to alleviate these symptoms in advanced PD. Yet the mechanism of action, especially the effects of STN-DBS on the availability of striatal dopamine transporter (DAT) as a marker of nigrostriatal nerve cell function, remains largely unknown. The aim of this study was therefore to evaluate whether 1) DAT availability changes within 1 year of STN-DBS and 2) the clinical outcome can be predicted based on preoperative DAT availability.METHODSTwenty-seven PD patients (mean age 62.7 ± 8.9 years; mean duration of illness 13.0 ± 4.9 years; PD subtypes: akinetic-rigid, n = 11; equivalence, n = 13; and tremor-dominant, n = 3) underwent [123I]FP-CIT SPECT preoperatively and after 1 year of STN-DBS. DAT availability as determined by the specific binding ratio (SBR) was assessed by volume of interest (VOI) analysis of the caudate nucleus and the putamen ipsilateral and contralateral to the clinically more affected side.RESULTSUnified Parkinson’s Disease Rating Scale (UPDRS) III scores improved significantly (mean preoperative on medication 25.6 ± 12.3, preoperative off medication 42.3 ± 15.2, postoperative on medication/off stimulation 41.4 ± 13.2, and postoperative on medication/on stimulation 16.1 ± 9.4; preoperative on medication vs postoperative on medication/on stimulation, p = 0.006), while the levodopa-equivalent daily dose was reduced (mean preoperative 957 ± 440 mg vs postoperative 313 ± 189 mg, p < 0.001). The SBR did not differ significantly before and 1 year after DBS, regardless of PD subtype. Preoperative DAT availability was not related to the change in UPDRS III score, but the change in DAT availability was significantly correlated with the change in UPDRS III score (contralateral head of the caudate VOI, p = 0.014; contralateral putamen VOI, p = 0.018).CONCLUSIONSOverall, DAT availability did not change significantly after 1 year of STN-DBS. However, on an individual basis, the improvement in UPDRS III score was associated with an increase in DAT availability, whereas DAT availability before STN-DBS surgery did not predict the clinical outcome. Whether a subtype-specific pattern of preoperative DAT availability can become a reliable predictor of successful STN-DBS must be evaluated in larger study cohorts.

scholarly journals Probing the striatal dopamine system for a putative neuroprotective effect of deep brain stimulation in Parkinson's disease

2018 ◽  
Vol 33 (4) ◽  
pp. 652-654 ◽  
Author(s):  
Gian Pal ◽  
Bichun Ouyang ◽  
Leo Verhagen ◽  
Geidy Serrano ◽  
Holly A. Shill ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Neuroprotective Effect ◽  
Striatal Dopamine ◽  
Dopamine System ◽  
Deep Brain

scholarly journals Intraoperative Characterization of Subthalamic Nucleus-to-Cortex Evoked Potentials in Parkinson’s Disease Deep Brain Stimulation

2021 ◽  
Vol 15 ◽  
Author(s):  
Lila H. Levinson ◽  
David J. Caldwell ◽  
Jeneva A. Cronin ◽  
Brady Houston ◽  
Steve I. Perlmutter ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Evoked Potentials ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
High Frequency ◽  
Therapeutic Effects ◽  
Stn Dbs ◽  
Deep Brain

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a clinically effective tool for treating medically refractory Parkinson’s disease (PD), but its neural mechanisms remain debated. Previous work has demonstrated that STN DBS results in evoked potentials (EPs) in the primary motor cortex (M1), suggesting that modulation of cortical physiology may be involved in its therapeutic effects. Due to technical challenges presented by high-amplitude DBS artifacts, these EPs are often measured in response to low-frequency stimulation, which is generally ineffective at PD symptom management. This study aims to characterize STN-to-cortex EPs seen during clinically relevant high-frequency STN DBS for PD. Intraoperatively, we applied STN DBS to 6 PD patients while recording electrocorticography (ECoG) from an electrode strip over the ipsilateral central sulcus. Using recently published techniques, we removed large stimulation artifacts to enable quantification of STN-to-cortex EPs. Two cortical EPs were observed – one synchronized with DBS onset and persisting during ongoing stimulation, and one immediately following DBS offset, here termed the “start” and the “end” EPs respectively. The start EP is, to our knowledge, the first long-latency cortical EP reported during ongoing high-frequency DBS. The start and end EPs differ in magnitude (p &lt; 0.05) and latency (p &lt; 0.001), and the end, but not the start, EP magnitude has a significant relationship (p &lt; 0.001, adjusted for random effects of subject) to ongoing high gamma (80–150 Hz) power during the EP. These contrasts may suggest mechanistic or circuit differences in EP production during the two time periods. This represents a potential framework for relating DBS clinical efficacy to the effects of a variety of stimulation parameters on EPs.

Comparison of Subthalamic Nucleus and Globus Pallidus Deep Brain Stimulation in Parkinson’s Disease: A Systematic Review

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Azari H ◽  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Adverse Effects ◽  
Globus Pallidus ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Stn Dbs ◽  
Deep Brain

Background: Deep Brain Stimulation (DBS) is regarded as a viable therapeutic choice for Parkinson’s Disease (PD). The two most common sites for DBS are the Subthalamic Nucleus (STN) and Globus Pallidus (GPi). In this study, the clinical effectiveness of these two targets was compared. Methods: A systematic literature search in electronic databases were restricted to English language publications 2010 to 2021. Specified MeSH terms were searched in all databases. Studies that evaluated the Unified Parkinson’s Disease Rating Scale (UPDRS) III were selected by meeting the following criteria: (1) had at least three months follow-up period; (2) compared both GPi and STN DBS; (3) at least five participants in each group; (4) conducted after 2010. Study quality assessment was performed using the Modified Jadad Scale. Results: 3577 potentially relevant articles were identified 3569 were excluded based on title and abstract, duplicate and unsuitable article removal. Eight articles satisfied the inclusion criteria and were scrutinized (458 PD patients). Majority of studies reported no statistically significant between-group difference for improvements in UPDRS III scores. Conclusions: Although there were some results in terms of action tremor, rigidity, and urinary symptoms, which indicated that STN DBS might be a better choice or regarding the adverse effects, GPi seemed better; but it cannot be concluded that one target is superior. Other larger randomized clinical trials with longer follow-up periods and control groups are needed to decide which target is more efficient for stimulation and imposes fewer adverse effects on the patients.

Clinical outcomes following awake and asleep deep brain stimulation for Parkinson disease

2018 ◽  
Vol 130 (1) ◽  
pp. 109-120 ◽  
Author(s):  
Tsinsue Chen ◽  
Zaman Mirzadeh ◽  
Kristina M. Chapple ◽  
Margaret Lambert ◽  
Holly A. Shill ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Parkinson Disease ◽  
Clinical Outcomes ◽  
Brain Stimulation ◽  
Stn Dbs ◽  
Deep Brain

OBJECTIVERecent studies have shown similar clinical outcomes between Parkinson disease (PD) patients treated with deep brain stimulation (DBS) under general anesthesia without microelectrode recording (MER), so-called “asleep” DBS, and historical cohorts undergoing “awake” DBS with MER guidance. However, few studies include internal controls. This study aims to compare clinical outcomes after globus pallidus internus (GPi) and subthalamic nucleus (STN) DBS using awake and asleep techniques at a single institution.METHODSPD patients undergoing awake or asleep bilateral GPi or STN DBS were prospectively monitored. The primary outcome measure was stimulation-induced change in motor function off medication 6 months postoperatively, measured using the Unified Parkinson’s Disease Rating Scale part III (UPDRS-III). Secondary outcomes included change in quality of life, measured by the 39-item Parkinson’s Disease Questionnaire (PDQ-39), change in levodopa equivalent daily dosage (LEDD), stereotactic accuracy, stimulation parameters, and adverse events.RESULTSSix-month outcome data were available for 133 patients treated over 45 months (78 GPi [16 awake, 62 asleep] and 55 STN [14 awake, 41 asleep]). UPDRS-III score improvement with stimulation did not differ between awake and asleep groups for GPi (awake, 20.8 points [38.5%]; asleep, 18.8 points [37.5%]; p = 0.45) or STN (awake, 21.6 points [40.3%]; asleep, 26.1 points [48.8%]; p = 0.20) targets. The percentage improvement in PDQ-39 and LEDD was similar for awake and asleep groups for both GPi (p = 0.80 and p = 0.54, respectively) and STN cohorts (p = 0.85 and p = 0.49, respectively).CONCLUSIONSIn PD patients, bilateral GPi and STN DBS using the asleep method resulted in motor, quality-of-life, and medication reduction outcomes that were comparable to those of the awake method.

scholarly journals Depression and Anxiety Following Deep Brain Stimulation in Parkinson’s Disease: Systematic Review and Meta-Analysis

2014 ◽  
Vol 27 (3) ◽  
pp. 372 ◽  
Author(s):  
Maria Inês Couto ◽  
Ana Monteiro ◽  
Ana Oliveira ◽  
Nuno Lunet ◽  
João Massano
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Depressive Symptoms ◽  
Deep Brain Stimulation ◽  
Medical Treatment ◽  
Brain Stimulation ◽  
Meta Analysis ◽  
Short Term ◽  
Stn Dbs ◽  
Deep Brain

<p><strong>Introduction:</strong> Deep brain stimulation (DBS) is effective in advanced Parkinson’s disease (PD), improving motor symptoms, fluctuations and quality of life. However, adverse psychiatric outcomes have been reported, albeit variably and in an unstandardized fashion. We aimed to summarize the published evidence on the outcomes of anxiety and depressive symptoms in Parkinson’s disease patients following DBS, through systematic review and meta-analysis.<br /><strong>Material and Methods:</strong> PubMed was searched until May 2012 to identify studies assessing anxiety and depressive symptoms in PD patients who underwent bilateral DBS of the subthalamic nucleus (STN) or globus pallidus internus (GPi). Random effects metaanalyses were conducted for groups of at least three studies that were homogeneous regarding the design and the instruments used.<br /><strong>Results:</strong> 63 references were selected; 98.4% provided data on depression, and 38.1% on anxiety assessment scales. Two studies did not discriminate the target; from the remaining 61 references, short-term evaluation was performed in 37 (60.7%), mid-term in 36 (59.0%) and long-term in 5 (8.2%). Data on pre to postop variation was available in 57 (93.4%) reports and 16 (26.2%) presented STNDBS versus different comparison groups: GPi-DBS (n = 4 studies, 25.0%), eligible for surgery (n = 6, 37.5%), and medical treatment (n = 7, 43.8%).<br /><strong>Discussion:</strong> Improvement of depression and anxiety is apparent after DBS, more pronounced in the short-term, an effect that seems to wane in later assessments. Concerning depression, STN-DBS shows superiority against medical treatment, but not when compared to eligible for surgery control groups. The opposite is apparent for anxiety, as results favor medical treatment over STN-DBS, and STNDBS over eligible for surgery control group. Superiority of one target over the other is not evident from the results, but data slightly favors GPi for both outcomes.<br /><strong>Conclusion:</strong> The pattern and course of depressive symptoms and anxiety following DBS in PD is not clear, although both seem to improve in the short-term, especially depression following STN-DBS. Results are highly heterogeneous. Efforts should be carried out to standardize assessment procedures across centers.<br /><strong>Keywords:</strong> Parkinson’s Disease; Deep Brain Stimulation; Anxiety; Depression; Meta-Analysis.</p>

Apathy in patients with Parkinson’s disease following deep brain stimulation of the subthalamic nucleus

CNS Spectrums ◽  
2016 ◽  
Vol 21 (3) ◽  
pp. 258-264 ◽  
Author(s):  
Isabel Hindle Fisher ◽  
Hardev S. Pall ◽  
Rosalind D. Mitchell ◽  
Jamilla Kausar ◽  
Andrea E. Cavanna
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Rating Scale ◽  
Control Group ◽  
Stn Dbs ◽  
Deep Brain ◽  
Stimulation Of

ObjectiveApathy has been reported as a possible adverse effect of deep brain stimulation of the subthalamic nucleus (STN-DBS). We investigated the prevalence and severity of apathy in 22 patients with Parkinson’s disease (PD) who underwent STN-DBS, as well as the effects of apathy on quality of life (QOL).MethodsAll patients were assessed with the Lille Apathy Rating Scale (LARS), the Apathy Scale (AS), and the Parkinson’s Disease Questionnaire and were compared to a control group of 38 patients on pharmacotherapy alone.ResultsThere were no significant differences in the prevalence or severity of apathy between patients who had undergone STN-DBS and those on pharmacotherapy alone. Significant correlations were observed between poorer QOL and degree of apathy, as measured by the LARS (p<0.001) and the AS (p=0.021). PD-related disability also correlated with both apathy ratings (p<0.001 and p=0.017, respectively).ConclusionOur findings suggest that STN-DBS is not necessarily associated with apathy in the PD population; however, more severe apathy appears to be associated with a higher level of disability due to PD and worse QOL, but no other clinico-demographic characteristics.

scholarly journals Brain energization in response to deep brain stimulation of subthalamic nuclei in Parkinson's disease

2011 ◽  
Vol 31 (7) ◽  
pp. 1612-1622 ◽  
Author(s):  
Gaëtan Garraux ◽  
Mohamed A Bahri ◽  
Christian Lemaire ◽  
Christian Degueldre ◽  
Eric Salmon ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Brain Activity ◽  
Standardized Uptake Value ◽  
Target Area ◽  
Caudate Nuclei ◽  
Stn Dbs ◽  
Deep Brain

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment in a subgroup of medically refractory patients with Parkinson's disease (PD). Here, we compared resting-state 18F-fluorodeoxyglucose (FDG) positron emission tomography images in the stimulator off (DBS_OFF) and on (DBS_ON) conditions in eight PD patients in an unmedicated state, on average 2 years after bilateral electrode implantation. Global standardized uptake value (SUV) significantly increased by ∼11% in response to STN-DBS. To avoid any bias in the voxel-based analysis comparing DBS_ON and DBS_OFF conditions, individual scan intensity was scaled to a region where FDG-SUV did not differ significantly between conditions. The resulting FDG-SUV ratio (FDG-SUVR) was found to increase in many regions in response to STN-DBS including the target area of surgery, caudate nuclei, primary sensorimotor, and associative cortices. Contrary to previous studies, we could not find any regional decrease in FDG-SUVR. These findings were indirectly supported by comparing the extent of areas with depressed FDG-SUVR in DBS_OFF and DBS_ON relatively to 10 normal controls. Altogether, these novel results support the prediction that the effect of STN-DBS on brain activity in PD is unidirectional and consists in an increase in many subcortical and cortical regions.

Clinical Motor Outcome of Bilateral Subthalamic Nucleus Deep-Brain Stimulation for Parkinson's Disease Using Image-Guided Frameless Stereotaxy

Neurosurgery ◽  
2010 ◽  
Vol 67 (4) ◽  
pp. 1088-1093 ◽  
Author(s):  
Helen Brontë-Stewart ◽  
Stephanie Louie ◽  
Sara Batya ◽  
Jaimie M Henderson
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Neurosurgical Procedures ◽  
Image Guided ◽  
Delayed Hemorrhage ◽  
Stn Dbs ◽  
Deep Brain

Abstract BACKGROUND: Image-guided neuronavigation has largely replaced stereotactic frames when precise, real-time anatomic localization is required during neurosurgical procedures. However, some procedures, including placement of deep-brain stimulation (DBS) leads for the treatment of movement disorders, are still performed using frame-based stereotaxy. Despite the demonstration of comparable accuracy between frame-based and “frameless” image-guided approaches, the clinical efficacy of frameless DBS placement has never been reported. OBJECTIVE: To analyze the outcomes of subthalamic nucleus (STN) DBS using the frameless technique for the treatment of Parkinson's disease (PD). METHODS: Of 31 subjects (20 men) with PD for 10 ± 4 years, 28 had bilateral STN DBS and 3 had unilateral STN DBS. The Unified Parkinson's Disease Rating Scale (UPDRS) motor scale (III) and total medication doses were assessed before surgery on and off medication and off medication/ON DBS (off/ON) after 6 to 12 months of STN DBS. RESULTS: There was a 58% improvement from bilateral STN DBS in the UPDRS III (40 ± 16 preoperatively off, 17 ± 11 off/ON) 9.6 ± 1.9 months after surgery (P &lt; .001). This compared favorably with the published outcomes using the frame-based technique. All motor subscores improved significantly (P &lt; .01). The mean reduction in medication was 50%. No intraoperative complications occurred, but one subject with hypertension died of a delayed hemorrhage postoperatively. Two subjects developed postoperative infections that required lead removal and antibiotics. CONCLUSIONS: Bilateral STN DBS for PD performed by an experienced team using a frameless approach results in outcomes comparable to those reported with the use of the frame-based technique.

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