| 1. |
- Akbarian-Tefaghi, Ladan, et al.
(författare)
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Refining the Deep Brain Stimulation Target within the Limbic Globus Pallidus Internus for Tourette Syndrome
- 2017
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Ingår i: Stereotactic and Functional Neurosurgery. - : S. Karger. - 1011-6125 .- 1423-0372. ; 95:4, s. 251-258
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Deep brain stimulation (DBS) in patients with severe, refractory Tourette syndrome (TS) has demonstrated promising but variable results thus far. The thalamus and anteromedial globus pallidus internus (amGPi) have been the most commonly stimulated sites within the cortico-striato thalamic circuit, but an optimal target is yet to be elucidated.OBJECTIVES: This study of 15 patients with long-term amGPi DBS for severe TS investigated whether a specific anatomical site within the amGPi correlated with optimal clinical outcome for the measures of tics, obsessive compulsive behaviour (OCB), and mood.METHODS: Validated clinical assessments were used to measure tics, OCB, quality of life, anxiety, and depression before DBS and at the latest follow-up (17-82 months). Electric field simulations were created for each patient using information on electrode location and individual stimulation parameters. A subsequent regression analysis correlated these patient-specific simulations to percentage changes in outcome measures in order to identify any significant voxels related to clinical improvement.RESULTS: A region within the ventral limbic GPi, specifically on the medial medullary lamina in the pallidum at the level of the AC-PC, was significantly associated with improved tics but not mood or OCB outcome.CONCLUSIONS: This study adds further support to the application of DBS in a tic-related network, though factors such as patient sample size and clinical heterogeneity remain as limitations and replication is required.
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| 2. |
- Barker, Roger A., et al.
(författare)
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Designing stem-cell-based dopamine cell replacement trials for Parkinson’s disease
- 2019
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 25, s. 1045-1053
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Tidskriftsartikel (refereegranskat)abstract
- Clinical studies of Parkinson’s disease (PD) using a dopamine cell replacment strategy have been tried for more than 30 years. The outcomes following transplantation of human fetal ventral mesencephalic tissue (hfVM) have been variable, with some patients coming off their anti-PD treatment for many years and others not responding and/or developing significant side effects, including graft-induced dyskinesia. This led to a re-appraisal of the best way to do such trials, which resulted in a new European-Union-funded allograft trial with fetal dopamine cells across several centers in Europe. This new trial, TRANSEURO (NCT01898390), is an open-label study in which some individuals in a large observational cohort of patients with mild PD who were undergoing identical assessments were randomly selected to receive transplants of hfVM. The TRANSEURO trial is currently ongoing as researchers have completed both recruitment into a large multicenter observational study of younger onset early-stage PD and transplantation of hfVM in 11 patients. While completion of TRANSEURO is not expected until 2021, we feel that sharing the rationale for the design of TRANSEURO, along with the lessons we have learned along the way, can help inform researchers and facilitate planning of transplants of dopamine-producing cells derived from human pluripotent stem cells for future clinical trials.
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| 3. |
- Cappon, Davide, et al.
(författare)
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Globus pallidal deep brain stimulation for Tourette syndrome : Effects on cognitive function
- 2019
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier. - 1353-8020 .- 1873-5126. ; 69, s. 14-18
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: In a double-blind randomized crossover trial, we previously established that bilateral deep brain stimulation of the anteromedial globus pallidus internus (GPiam-DBS) is effective in significantly reducing tic severity in patients with refractory Tourette syndrome (TS). Here, we report the effects of bilateral GPiam-DBS on cognitive function in 11 of the 13 patients who had participated in our double-blind cross-over trial of GPi-DBS.Methods: Patients were assessed at baseline (4 weeks prior to surgery) and at the end of each of the three-month blinded periods, with stimulation either ON or OFF. The patients were evaluated on tests of memory (California Verbal Learning Test-II (CVLT-II); Corsi blocks; Short Recognition Memory for Faces), executive function (D-KEFS Stroop color-word interference, verbal fluency, Trail-making test, Hayling Sentence Completion test), and attention (Paced Auditory Serial Addition Test, Numbers and Letters Test).Results: GPiam-DBS did not produce any significant change in global cognition. Relative to pre-operative baseline assessment verbal episodic memory on the CVLT-II and set-shifting on the Trail-making Test were improved with DBS OFF. Performance on the cognitive tests were not different with DBS ON versus DBS OFF. GPiam-DBS did not alter aspects of cognition that are impaired in TS such as inhibition on the Stroop interference task or the Hayling Sentence Completion test.Conclusions: This study extends previous findings providing data showing that GPiam-DBS does not adversely affect cognitive domains such as memory, executive function, verbal fluency, attention, psychomotor speed, and information processing. These results indicate that GPiam-DBS does not produce any cognitive deficits in TS.
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| 4. |
- Kefalopoulou, Zinovia, et al.
(författare)
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Long-term clinical outcome of fetal cell transplantation for Parkinson disease : two case reports
- 2014
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 71:1, s. 7-83
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Recent advances in stem cell technologies have rekindled an interest in the use of cell replacement strategies for patients with Parkinson disease. This study reports the very long-term clinical outcomes of fetal cell transplantation in 2 patients with Parkinson disease. Such long-term follow-up data can usefully inform on the potential efficacy of this approach, as well as the design of trials for its further evaluation.OBSERVATIONS: Two patients received intrastriatal grafts of human fetal ventral mesencephalic tissue, rich in dopaminergic neuroblasts, as restorative treatment for their Parkinson disease. To evaluate the very long-term efficacy of the grafts, clinical assessments were performed 18 and 15 years posttransplantation. Motor improvements gained gradually over the first postoperative years were sustained up to 18 years posttransplantation, while both patients have discontinued, and remained free of any, pharmacological dopaminergic therapy.CONCLUSIONS AND RELEVANCE: The results from these 2 cases indicate that dopaminergic cell transplantation can offer very long-term symptomatic relief in patients with Parkinson disease and provide proof-of-concept support for future clinical trials using fetal or stem cell therapies.
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| 5. |
- Loane, Clare, et al.
(författare)
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Aberrant nigral diffusion in Parkinson's disease : A longitudinal diffusion tensor imaging study
- 2016
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185. ; 31:7, s. 6-1020
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Measuring microstructure alterations with diffusion tensor imaging in PD is potentially a valuable tool to use as a biomarker for early diagnosis and to track disease progression. Previous studies have reported a specific decrease of nigral fractional anisotropy in PD. However, to date the effect of disease progression on nigral or striatal diffusion indices has not been fully explored.METHODS: We have conducted a cross-sectional and longitudinal diffusion tensor imaging study in 18 early stage, treated PD patients and 14 age-matched controls. PD patients were scanned on 2 occasions OFF medication, 19.3 months apart (standard deviation = 3.1 months). Longitudinal change of regional nigral and striatal measures of fractional anisotropy and mean diffusivity were calculated using a region-of-interest approach.RESULTS: Region-of-interest analysis demonstrated that at baseline, PD patients and controls did not differ in regard to diffusion indices in any region assessed. A significant difference of nigral fractional anisotropy and mean diffusivity between controls and PD patients at follow-up was detected and confirmed with longitudinal analysis within PD patients. Alterations in striatal regions were not detected in either group or over time.CONCLUSION: Our findings indicate that nigral diffusion measure may be a valuable measure of disease progression. In the future, larger longitudinal studies will confirm whether diffusion indices may serve as sensitive and clinically meaningful measures of disease progression in PD. © 2016 International Parkinson and Movement Disorder Society.
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| 6. |
- Martinez-Ramirez, Daniel, et al.
(författare)
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Efficacy and Safety of Deep Brain Stimulation in Tourette Syndrome : The International Tourette Syndrome Deep Brain Stimulation Public Database and Registry
- 2018
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Ingår i: JAMA Neurology. - : American Medical Association. - 2168-6149 .- 2168-6157. ; 75:3, s. 353-359
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Collective evidence has strongly suggested that deep brain stimulation (DBS) is a promising therapy for Tourette syndrome.OBJECTIVE To assess the efficacy and safety of DBS in a multinational cohort of patients with Tourette syndrome.DESIGN, SETTING, AND PARTICIPANTS The prospective International Deep Brain Stimulation Database and Registry included 185 patients with medically refractory Tourette syndrome who underwent DBS implantation from January 1, 2012, to December 31, 2016, at 31 institutions in 10 countries worldwide.EXPOSURES Patients with medically refractory symptoms received DBS implantation in the centromedian thalamic region (93 of 163 [57.1%]), the anterior globus pallidus internus (41 of 163 [25.2%]), the posterior globus pallidus internus (25 of 163 [15.3%]), and the anterior limb of the internal capsule (4 of 163 [2.5%]).MAIN OUTCOMES AND MEASURES Scores on the Yale Global Tic Severity Scale and adverse events.RESULTS The International Deep Brain Stimulation Database and Registry enrolled 185 patients (of 171 with available data, 37 females and 134 males; mean [SD] age at surgery, 29.1 [10.8] years [range, 13-58 years]). Symptoms of obsessive-compulsive disorder were present in 97 of 151 patients (64.2%) and 32 of 148 (21.6%) had a history of self-injurious behavior. The mean (SD) total Yale Global Tic Severity Scale score improved from 75.01 (18.36) at baseline to 41.19 (20.00) at 1 year after DBS implantation (P<.001). The mean (SD) motor tic subscore improved from 21.00 (3.72) at baseline to 12.91 (5.78) after 1 year (P <.001), and the mean (SD) phonic tic subscore improved from 16.82 (6.56) at baseline to 9.63 (6.99) at 1 year (P <.001). The overall adverse event rate was 35.4%(56 of 158 patients), with intracranial hemorrhage occurring in 2 patients (1.3%), infection in 4 patients with 5 events (3.2%), and lead explantation in 1 patient (0.6%). The most common stimulation-induced adverse effects were dysarthria (10 [6.3%]) and paresthesia (13 [8.2%]).CONCLUSIONS AND RELEVANCE Deep brain stimulationwas associated with symptomatic improvement in patients with Tourette syndrome but also with important adverse events. A publicly available website on outcomes of DBS in patients with Tourette syndrome has been provided.
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| 7. |
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| 8. |
- Skaramagkas, Vasileios, et al.
(författare)
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A Study on the Essential and Parkinson’s Arm Tremor Classification
- 2021
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Ingår i: Signals. - : Multidisciplinary Digital Publishing Institute (MDPI). - 2624-6120. ; 2:2, s. 201-224
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Tidskriftsartikel (refereegranskat)abstract
- In this article, the challenge of discriminating between essential and Parkinson’s tremor is addressed. Although a variety of methods have been proposed for diagnosing the severity of these highly occurring tremor types, their rapid and effective identification, especially in their early stages, proves particularly difficult and complicated due to their wide range of causes and similarity of symptoms. To this goal, a clinical analysis was performed, where a number of volunteers including essential and Parkinson’s tremor-diagnosed patients underwent a series of pre-defined motion patterns, during which a wearable sensing setup was used to measure their lower arm tremor characteristics from multiple selected points. Extracted features from the acquired accelerometer signals were used to train classification algorithms, including decision trees, discriminant analysis, support vector machine (SVM), K-nearest neighbor (KNN) and ensemble learning algorithms, for providing a comparative study and evaluating the potential of utilizing machine learning to accurately discriminate among different tremor types. Overall, SVM related classifiers proved to be the most successful in terms of classifying between Parkinson’s, essential and no tremor diagnosed with percentages reaching up to 100% for a single accelerometer measurement at the metacarpal area. In general and in motion while holding an object position, Coarse Gaussian SVM classifier reached 82.62% accuracy.
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| 9. |
- Skaramagkas, Vasileios, et al.
(författare)
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Towards Differential Diagnosis of Essential and Parkinson's Tremor via Machine Learning
- 2020
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Ingår i: 2020 28th Mediterranean Conference on Control and Automation (MED). - : IEEE. ; , s. 782-787
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Konferensbidrag (refereegranskat)abstract
- In this article, the challenge of identifying between Essential and Parkinson's tremor is addressed. To this goal, a clinical analysis was performed, where a number of volunteers including Essential and Parkinson's tremor-diagnosed patients underwent a series of pre-defined motion patterns, during which a wearable sensing setup was used to measure their lower arm tremor characteristics from multiple selected points. Extracted features from the acquired accelerometer signals were used to train classification algorithms, including decision trees, discriminant analysis, support vector machine (SVM), K-nearest neighbor (KNN) and ensemble learning algorithms, for providing a comparative study and evaluating the potential of utilizing machine learning to accurately identify between different tremor types.
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| 10. |
- Skaramagkas, Vasileios, et al.
(författare)
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Towards differential diagnosis of essential and parkinson's tremor via machine learning
- 2020
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Ingår i: 2020 28th Mediterranean Conference on Control and Automation (MED). - : Institute of Electrical and Electronics Engineers (IEEE). ; , s. 782-787
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Konferensbidrag (refereegranskat)abstract
- In this article, the challenge of identifying between Essential and Parkinson's tremor is addressed. To this goal, a clinical analysis was performed, where a number of volunteers including Essential and Parkinson's tremor-diagnosed patients underwent a series of pre-defined motion patterns, during which a wearable sensing setup was used to measure their lower arm tremor characteristics from multiple selected points. Extracted features from the acquired accelerometer signals were used to train classification algorithms, including decision trees, discriminant analysis, support vector machine (SVM), K-nearest neighbor (KNN) and ensemble learning algorithms, for providing a comparative study and evaluating the potential of utilizing machine learning to accurately identify between different tremor types.
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