| 1. |
- Wirth, Thomas, et al.
(author)
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Clinical outcomes after MRI connectivity-guided radiofrequency thalamotomy for tremor
- 2024
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In: Journal of Neurosurgery. - : American Association of Neurological Surgeons. - 0022-3085 .- 1933-0693. ; 140:4, s. 1148-1154
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Radiofrequency thalamotomy (RF-T) is an established treatment for refractory tremor. It is unclear whether connectivity-guided targeting strategies could further augment outcomes. The aim of this study was to evaluate the efficacy and safety of MRI connectivity-guided RF-T in severe tremor.METHODS: Twenty-one consecutive patients with severe tremor (14 with essential tremor [ET], 7 with Parkinson's disease [PD]) underwent unilateral RF-T at a single institution between 2017 and 2020. Connectivity-derived thalamic segmentation was used to guide targeting. Changes in the Fahn-Tolosa-Marin Rating Scale (FTMRS) were recorded in treated and nontreated hands as well as procedure-related side effects.RESULTS: Twenty-three thalamotomies were performed (with 2 patients receiving a repeated intervention). The mean postoperative assessment time point was 14.1 months. Treated-hand tremor scores improved by 63.8%, whereas nontreated-hand scores deteriorated by 10.1% (p < 0.01). Total FTMRS scores were significantly better at follow-up compared with baseline (mean 34.7 vs 51.7, p = 0.016). Baseline treated-hand tremor severity (rho = 0.786, p < 0.01) and total FTMRS score (rho = 0.64, p < 0.01) best correlated with tremor improvement. The most reported side effect was mild gait ataxia (n = 11 patients).CONCLUSIONS: RF-T guided by connectivity-derived segmentation is a safe and effective option for severe tremor in both PD and ET.
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| 2. |
- Wirth, Thomas, et al.
(author)
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Parkinson's disease tremor differentially responds to levodopa and subthalamic stimulation
- 2023
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In: Movement Disorders Clinical Practice. - : John Wiley & Sons. - 2330-1619. ; 10:11, s. 1639-1649
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Journal article (peer-reviewed)abstract
- Background: Tremor in Parkinson's disease (PD) has an inconsistent response to levodopa and subthalamic deep brain stimulation (STN-DBS).Objectives: To identify predictive factors of PD tremor responsiveness to levodopa and STN-DBS.Material and Methods: PD patients with upper limb tremor who underwent STN-DBS were included. The levodopa responsiveness of tremor (overall, postural, and rest sub-components), was assessed using the relevant Unified Parkinson's Disease Rating Scale-III items performed during the preoperative assessment. Post-surgical outcomes were similarly assessed ON and OFF stimulation. A score for the rest/postural tremor ratio was used to determine the influence of rest and postural tremor severity on STN-DBS outcome. Factors predictive of tremor responsiveness were determined using multiple linear regression modeling. Volume of tissue activated measurement coupled to voxel-based analysis was performed to identify anatomical clusters associated with motor symptoms improvement.Results: One hundred and sixty five patients were included in this study. Male gender was negatively correlated with tremor responsiveness to levodopa, whereas the ratio of rest/postural tremor was positively correlated with both levodopa responsiveness and STN-DBS tremor outcome. Clusters corresponding to improvement of tremor were in the subthalamic nucleus, the zona incerta and the thalamus, whereas clusters corresponding to improvement for akinesia and rigidity were located within the subthalamic nucleus.Conclusion: More severe postural tremor and less severe rest tremor were associated with both poorer levodopa and STN-DBS response. The different locations of clusters associated with best correction of tremor and other parkinsonian features suggest that STN-DBS effect on PD symptoms is underpinned by the modulation of different networks.
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| 3. |
- Akram, Harith, et al.
(author)
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Connectivity derived thalamic segmentation in deep brain stimulation for tremor
- 2018
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In: NeuroImage. - : Elsevier. - 2213-1582. ; 18, s. 130-142
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Journal article (peer-reviewed)abstract
- The ventral intermediate nucleus (VIM) of the thalamus is an established surgical target for stereotactic ablation and deep brain stimulation (DBS) in the treatment of tremor in Parkinson's disease (PD) and essential tremor (ET). It is centrally placed on a cerebello-thalamo-cortical network connecting the primary motor cortex, to the dentate nucleus of the contralateral cerebellum through the dentato-rubro-thalamic tract (DRT). The VIM is not readily visible on conventional MR imaging, so identifying the surgical target traditionally involved indirect targeting that relies on atlas-defined coordinates. Unfortunately, this approach does not fully account for individual variability and requires surgery to be performed with the patient awake to allow for intraoperative targeting confirmation. The aim of this study is to identify the VIM and the DRT using probabilistic tractography in patients that will undergo thalamic DBS for tremor. Four male patients with tremor dominant PD and five patients (three female) with ET underwent high angular resolution diffusion imaging (HARDI) (128 diffusion directions, 1.5 mm isotropic voxels and b value = 1500) preoperatively. Patients received VIM-DBS using an MR image guided and MR image verified approach with indirect targeting. Postoperatively, using parallel Graphical Processing Unit (GPU) processing, thalamic areas with the highest diffusion connectivity to the primary motor area (M1), supplementary motor area (SMA), primary sensory area (S1) and contralateral dentate nucleus were identified. Additionally, volume of tissue activation (VTA) corresponding to active DBS contacts were modelled. Response to treatment was defined as 40% reduction in the total Fahn-Tolosa-Martin Tremor Rating Score (FTMTRS) with DBS-ON, one year from surgery. Three out of nine patients had a suboptimal, long-term response to treatment. The segmented thalamic areas corresponded well to anatomically known counterparts in the ventrolateral (VL) and ventroposterior (VP) thalamus. The dentate-thalamic area, lay within the M1-thalamic area in a ventral and lateral location. Streamlines corresponding to the DRT connected M1 to the contralateral dentate nucleus via the dentate-thalamic area, clearly crossing the midline in the mesencephalon. Good response was seen when the active contact VTA was in the thalamic area with highest connectivity to the contralateral dentate nucleus. Non-responders had active contact VTAs outside the dentate-thalamic area. We conclude that probabilistic tractography techniques can be used to segment the VL and VP thalamus based on cortical and cerebellar connectivity. The thalamic area, best representing the VIM, is connected to the contralateral dentate cerebellar nucleus. Connectivity based segmentation of the VIM can be achieved in individual patients in a clinically feasible timescale, using HARDI and high performance computing with parallel GPU processing. This same technique can map out the DRT tract with clear mesencephalic crossing.
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| 4. |
- Akram, Harith, et al.
(author)
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L-Dopa Responsiveness Is Associated With Distinctive Connectivity Patterns in Advanced Parkinson's Disease
- 2017
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In: Movement Disorders. - : Wiley-Blackwell. - 0885-3185 .- 1531-8257. ; 32:6, s. 874-883
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Journal article (peer-reviewed)abstract
- Background: Neuronal loss and dopamine depletion alter motor signal processing between cortical motor areas, basal ganglia, and the thalamus, resulting in the motor manifestations of Parkinson's disease. Dopamine replacement therapy can reverse these manifestations with varying degrees of improvement. Methods: To evaluate functional connectivity in patients with advanced Parkinson's disease and changes in functional connectivity in relation to the degree of response to L-dopa, 19 patients with advanced Parkinson's disease underwent resting-state functional magnetic resonance imaging in the on-medication state. Scans were obtained on a 3-Tesla scanner in 3x3x2.5mm(3) voxels. Seed-based bivariate regression analyses were carried out with atlas-defined basal ganglia regions as seeds, to explore relationships between functional connectivity and improvement in the motor section of the UPDRS-III following an L-dopa challenge. False discovery rate-corrected P was set at < 0.05 for a 2-tailed t test. Results: A greater improvement in UPDRS-III scores following L-dopa administration was characterized by higher resting-state functional connectivity between the prefrontal cortex and the striatum (P=0.001) and lower resting-state functional connectivity between the pallidum (P=0.001), subthalamic nucleus (P=0.003), and the paracentral lobule (supplementary motor area, mesial primary motor, and primary sensory areas). Conclusions: Our findings show characteristic basal ganglia resting-state functional connectivity patterns associated with different degrees of L-dopa responsiveness in patients with advanced Parkinson's disease. L-Dopa exerts a graduated influence on remapping connectivity in distinct motor control networks, potentially explaining some of the variance in treatment response.
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| 5. |
- Akram, Harith, et al.
(author)
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Subthalamic deep brain stimulation sweet spots and hyperdirect cortical connectivity in Parkinson's disease
- 2017
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In: NeuroImage. - : Elsevier. - 1053-8119 .- 1095-9572. ; 158, s. 332-345
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Journal article (peer-reviewed)abstract
- Objectives: Firstly, to identify subthalamic region stimulation clusters that predict maximum improvement in rigidity, bradykinesia and tremor, or emergence of side-effects; and secondly, to map-out the cortical fingerprint, mediated by the hyperdirect pathways which predict maximum efficacy.Methods: High angular resolution diffusion imaging in twenty patients with advanced Parkinson's disease was acquired prior to bilateral subthalamic nucleus deep brain stimulation. All contacts were screened one-year from surgery for efficacy and side-effects at different amplitudes. Voxel-based statistical analysis of volumes of tissue activated models was used to identify significant treatment clusters. Probabilistic tractography was employed to identify cortical connectivity patterns associated with treatment efficacy.Results: All patients responded well to treatment (46% mean improvement off medication UPDRS-III [p < 0.0001]) without significant adverse events. Cluster corresponding to maximum improvement in tremor was in the posterior, superior and lateral portion of the nucleus. Clusters corresponding to improvement in bradykinesia and rigidity were nearer the superior border in a further medial and posterior location. The rigidity cluster extended beyond the superior border to the area of the zona incerta and Forel-H-2 field. When the clusters where averaged, the coordinates of the area with maximum overall efficacy was X = -10(-9.5), Y = -3(-1) and Z = -7(-3) in MNI(AC-PC) space. Cortical connectivity to primary motor area was predictive of higher improvement in tremor; whilst that to supplementary motor area was predictive of improvement in bradykinesia and rigidity; and connectivity to prefrontal cortex was predictive of improvement in rigidity.Interpretation: These findings support the presence of overlapping stimulation sites within the subthalamic nucleus and its superior border, with different cortical connectivity patterns, associated with maximum improvement in tremor, rigidity and bradykinesia.
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| 6. |
- Barker, Roger A., et al.
(author)
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Designing stem-cell-based dopamine cell replacement trials for Parkinson’s disease
- 2019
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 25, s. 1045-1053
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Journal article (peer-reviewed)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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| 7. |
- Cappon, Davide, et al.
(author)
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Deep Brain Stimulation of the Nucleus Basalis of Meynert for Parkinson's Disease Dementia : A 36 Months Follow Up Study
- 2022
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In: Movement Disorders Clinical Practice. - : John Wiley & Sons. - 2330-1619. ; 9:6, s. 765-774
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Journal article (peer-reviewed)abstract
- Background: Degeneration of the nucleus basalis of Meynert (NBM) and cortical cholinergic dysfunction are hallmarks of Parkinson's disease dementia (PDD). There is no effective therapy for PDD. Deep brain stimulation of the NBM (NBM-DBS) has been trialed as a potential treatment.Objective: Our primary aim was to evaluate the sustained tolerability of NBM-DBS in PDD, and its impact on global cognition, behavioral symptoms, quality of life and caregiver burden and distress. Second, we aimed to determine whether baseline measures of arousal, alertness, and attention were predictive of the three year response to NBM-DBS in PDD patients.Methods: Five of the six PDD patients who completed the baseline assessment participated in a 3 year follow up assessment. We assessed the participants after three years of NBM-DBS on the Mini Mental State Examination, Dementia Rating Scale-2, Blessed Dementia Rating Scale, Neuropsychiatric Inventory, and the SF36.Results: The five patients showed varying trajectories of cognitive decline, with two showing a slower progression over the three-year follow-up period. A slower progression of decline on global cognition was associated with higher baseline accuracy on the Posner covert orienting of attention test, and less daytime sleepiness.Conclusions: Whether slower progression of cognitive decline in two patients was in any way related to individual variability in responsiveness to NBM-DBS requires confirmation in a larger series including an unoperated PDD control group. Higher accuracy in covertly orienting attention and better sleep quality at baseline were associated with better cognitive outcomes at 36 months assessment. These results require validation in future studies with larger samples.
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| 8. |
- Cappon, Davide, et al.
(author)
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Globus pallidal deep brain stimulation for Tourette syndrome : Effects on cognitive function
- 2019
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In: Parkinsonism & Related Disorders. - : Elsevier. - 1353-8020 .- 1873-5126. ; 69, s. 14-18
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Journal article (peer-reviewed)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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| 9. |
- Dayal, Viswas, et al.
(author)
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Pedunculopontine nucleus deep brain stimulation for parkinsonian disorders : a case series
- 2021
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In: Stereotactic and Functional Neurosurgery. - : S. Karger. - 1011-6125 .- 1423-0372. ; 99:4, s. 287-294
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Journal article (peer-reviewed)abstract
- Background: Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) has been investigated for the treatment of levodopa-refractory gait dysfunction in parkinsonian disorders, with equivocal results so far.Objectives: To summarize the clinical outcomes of PPN-DBS-treated patients at our centre and elicit any patterns that may guide future research.Materials and Methods: Pre- and post-operative objective overall motor and gait subsection scores as well as patient-reported outcomes were recorded for 6 PPN-DBS-treated patients, 3 with Parkinson's disease (PD), and 3 with progressive supranuclear palsy (PSP). Electrodes were implanted unilaterally in the first 3 patients and bilaterally in the latter 3, using an MRI-guided MRI-verified technique. Stimulation was initiated at 20-30 Hz and optimized in an iterative manner.Results: Unilaterally treated patients did not demonstrate significant improvements in gait questionnaires, UPDRS-III or PSPRS scores or their respective gait subsections. This contrasted with at least an initial response in bilaterally treated patients. Diurnal cycling of stimulation in a PD patient with habituation to the initial benefit reproduced substantial improvements in freezing of gait (FOG) 3 years post-operatively. Among the PSP patients, 1 with a parkinsonian subtype had a sustained improvement in FOG while another with Richardson syndrome (PSP-RS) did not benefit.Conclusions: PPN-DBS remains an investigational treatment for levodopa-refractory FOG. This series corroborates some previously reported findings: bilateral stimulation may be more effective than unilateral stimulation; the response in PSP patients may depend on the disease subtype; and diurnal cycling of stimulation to overcome habituation merits further investigation.
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| 10. |
- Dayal, Viswas, et al.
(author)
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Short Versus Conventional Pulse-Width Deep Brain Stimulation in Parkinson's Disease : A Randomized Crossover Comparison
- 2020
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In: Movement Disorders. - : John Wiley & Sons. - 0885-3185 .- 1531-8257. ; 35:1, s. 101-108
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Journal article (peer-reviewed)abstract
- Background: Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective therapy for selected Parkinson's disease patients with motor fluctuations, but can adversely affect speech and axial symptoms. The use of short pulse width (PW) has been shown to expand the therapeutic window acutely, but its utility in reducing side effects in chronic STN-DBS patients has not been evaluated. Objective To compare the effect of short PW settings using 30-mu s with conventional 60-mu s settings on stimulation-induced dysarthria in Parkinson's disease patients with previously implanted STN-DBS systems.Methods: In this single-center, double-blind, randomized crossover trial, we assigned 16 Parkinson's disease patients who had been on STN-DBS for a mean of 6.5 years and exhibited moderate dysarthria to 30-mu s or 60-mu s settings for 4 weeks followed by the alternative PW setting for a further 4 weeks. The primary outcome was difference in dysarthric speech measured by the Sentence Intelligibility Test between study baseline and the 2 PW conditions. Secondary outcomes included motor, nonmotor, and quality of life measures.Results: There was no difference in the Sentence Intelligibility Test scores between baseline and the 2 treatment conditions (P = 0.25). There were also no differences noted in motor, nonmotor, or quality of life scores. The 30-mu s settings were well tolerated, and adverse event rates were similar to those at conventional PW settings. Post hoc analysis indicated that patients with dysarthria and a shorter duration of DBS may be improved by short PW stimulation.Conclusions: Short PW settings using 30 mu s did not alter dysarthric speech in chronic STN-DBS patients. A future study should evaluate whether patients with shorter duration of DBS may be helped by short PW settings.
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| 11. |
- Fasano, Alfonso, et al.
(author)
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Management of Advanced Therapies in Parkinson's Disease Patients in Times of Humanitarian Crisis : The COVID-19 Experience
- 2020
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In: Movement Disorders Clinical Practice. - : Wiley. - 2330-1619. ; 7:4, s. 361-372
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Research review (peer-reviewed)abstract
- Background: Although the COVID-19 pandemic is affecting a relatively small proportion of the global population, its effects have already reached everyone. The pandemic has the potential to differentially disadvantage chronically ill patients, including those with Parkinson's disease (PD). The first health care reaction has been to limit access to clinics and neurology wards to preserve fragile patients with PD from being infected. In some regions, the shortage of medical staff has also forced movement disorders neurologists to provide care for patients with COVID-19. Objective: To share the experience of various movement disorder neurologists operating in different world regions and provide a common approach to patients with PD, with a focus on those already on advanced therapies, which may serve as guidance in the current pandemic and for emergency situations that we may face in the future. Conclusion: Most of us were unprepared to deal with this condition given that in many health care systems, telemedicine has been only marginally available or only limited to email or telephone contacts. In addition, to ensure sufficient access to intensive care unit beds, most elective procedures (including deep brain stimulation or the initiation of infusion therapies) have been postponed. We all hope there will soon be a time when we will return to more regular hospital schedules. However, we should consider this crisis as an opportunity to change our approach and encourage our hospitals and health care systems to facilitate the remote management of chronic neurological patients, including those with advanced PD.
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| 12. |
- Foltynie, Thomas, et al.
(author)
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Surgical management of Parkinson's disease
- 2010
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In: Expert review of neurotherapeutics. - : Informa UK Limited. - 1744-8360 .- 1473-7175. ; 10:6, s. 903-914
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Journal article (peer-reviewed)abstract
- There has been a renaissance in the surgical treatment of Parkinson's disease (PD) over the last 15-20 years as a result of the long-term complications of L-DOPA use. The current cornerstone of surgical treatment for PD is high-frequency deep-brain stimulation (DBS) of the subthalamic nucleus (STN) using implantable electrodes and an implantable pulse generator/battery. Among well-selected patients, that is, patients with idiopathic PD, L-DOPA-responsive symptoms and no significant psychiatric comorbidities or cognitive decline, STN DBS can provide improvements in motor symptoms and quality of life, with low risks of adverse effects. In this article, we briefly describe the evolution of surgical treatments for PD, and the rationale for current DBS procedures. We also provide details of our practice, including patient selection, surgical technique and postoperative stimulation programming and medication adjustment. Current and possible future alternatives to DBS of the STN are also discussed.
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| 13. |
- Gonzalez-Robles, Cristina, et al.
(author)
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Embedding Patient Input in Outcome Measures for Long-Term Disease-Modifying Parkinson Disease Trials
- 2024
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In: Movement Disorders. - 0885-3185 .- 1531-8257. ; 39:2, s. 433-438
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Journal article (peer-reviewed)abstract
- Background: Clinical trials of disease-modifying therapies in PD require valid and responsive primary outcome measures that are relevant to patients. Objectives: The objective is to select a patient-centered primary outcome measure for disease-modification trials over three or more years. Methods: Experts in Parkinson's disease (PD), statistics, and health economics and patient and public involvement and engagement (PPIE) representatives reviewed and discussed potential outcome measures. A larger PPIE group provided input on their key considerations for such an endpoint. Feasibility, clinimetric properties, and relevance to patients were assessed and synthesized. Results: Although initial considerations favored the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III in Off, feasibility, PPIE input, and clinimetric properties supported the MDS-UPDRS Part II. However, PPIE input also highlighted the importance of nonmotor symptoms, especially in the longer term, leading to the selection of the MDS-UPDRS Parts I + II sum score. Conclusions: The MDS-UPDRS Parts I + II sum score was chosen as the primary outcome for large 3-year disease-modification trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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| 14. |
- Gonzalez-Robles, Cristina, et al.
(author)
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Outcome Measures for Disease-Modifying Trials in Parkinson's Disease: Consensus Paper by the EJS ACT-PD Multi-Arm Multi-Stage Trial Initiative
- 2023
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In: JOURNAL OF PARKINSONS DISEASE. - 1877-7171 .- 1877-718X. ; 13:6, s. 1013-1035
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Journal article (peer-reviewed)abstract
- Background: Multi-arm, multi-stage (MAMS) platform trials can accelerate the identification of disease-modifying treatments for Parkinson's disease (PD) but there is no current consensus on the optimal outcome measures (OM) for this approach. Objective: To provide an up-to-date inventory of OM for disease-modifying PD trials, and a framework for future selection of OM for such trials. Methods: As part of the Edmond J Safra Accelerating Clinical Trials in Parkinson Disease (EJS ACT-PD) initiative, an expert group with Patient and Public Involvement and Engagement (PPIE) representatives' input reviewed and evaluated available evidence on OM for potential use in trials to delay progression of PD. Each OM was ranked based on aspects such as validity, sensitivity to change, participant burden and practicality for a multi-site trial. Review of evidence and expert opinion led to the present inventory. Results: An extensive inventory ofOMwas created, divided into: general, motor and non-motor scales, diaries and fluctuation questionnaires, cognitive, disability and health-related quality of life, capability, quantitative motor, wearable and digital, combined, resource use, imaging and wet biomarkers, and milestone-based. A framework for evaluation of OM is presented to update the inventory in the future. PPIE input highlighted the need for OM which reflect their experience of disease progression and are applicable to diverse populations and disease stages. Conclusion: We present a range of OM, classified according to a transparent framework, to aid selection of OM for disease-modifying PD trials, whilst allowing for inclusion or re-classification of relevant OM as new evidence emerges.
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| 15. |
- Holl, Etienne M, et al.
(author)
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Improving targeting in image-guided frame-based deep brain stimulation
- 2010
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In: Neurosurgery. - 0148-396X .- 1524-4040. ; 67:2 Suppl, s. ons437-ons447
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Journal article (peer-reviewed)abstract
- After calibration of a systematic targeting error an MR image-guided stereotactic approach would be expected to deliver 97% of all electrodes to within 2 mm of the intended target point with a single brain pass.
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| 16. |
- Hyam, Jonathan A, et al.
(author)
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What You See Is What You Get : Lead Location Within Deep Brain Structures Is Accurately Depicted by Stereotactic Magnetic Resonance Imaging
- 2015
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In: Operative Neurosurgery. - : Lippincott Williams & Wilkins. - 2332-4252 .- 2332-4260. ; 11:3, s. 412-419
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Journal article (peer-reviewed)abstract
- BACKGROUND: Magnetic resonance imaging (MRI)-verified deep brain stimulation relies on the correct interpretation of stereotactic imaging documenting lead location in relation to visible anatomic target. However, it has been suggested that local signal distortion from the lead itself renders its depiction on MRI unreliable. OBJECTIVE: To compare lead location on stereotactic MRI with subsequent location of its brain track after removal. METHODS: Patients underwent deep brain stimulation with the use of MRI-guided and MRI-verified Leksell frame approach. Infection or suboptimal efficacy required lead removal and subsequent reimplantation by using the same technique. Postimplantation stereotactic MR images were analyzed. Lateral (x) and anteroposterior (y) distances from midcommissural point to center of the lead hypointensity were recorded at the anterior commissure-posterior commissure plane (pallidal electrode) or z = 24 (subthalamic electrode). Stereotactic MRI before the second procedure, x and y distances from the center of the visible lead track hypointensity to midcommissural point were independently recorded. Vectorial distance from center of the lead hypointensity to the center of its track was calculated. RESULTS: Sixteen electrode tracks were studied in 10 patients. Mean differences between lead artifact location and lead track location were: x coordinate 0.4 mm +/- 0.2; y coordinate 0.6 mm +/- 0.3. Mean vectorial distance was 0.7 mm +/- 0.2. CONCLUSION: Stereotactic distance between lead location and subsequent brain track location on MRI was small. The mean discrepancy was approximately half the deep brain stimulation lead width. This suggests that lead hypointensity seen on postimplantation MRI is indeed an accurate representation of its real location within deep brain structures.
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| 17. |
- Johnson, Kara A., et al.
(author)
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Basal Ganglia Pathways Associated With Therapeutic Pallidal Deep Brain Stimulation for Tourette Syndrome
- 2021
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In: Biological Psychiatry. - : Elsevier. - 2451-9022. ; 6:10, s. 961-972
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Journal article (peer-reviewed)abstract
- Background: Deep brain stimulation (DBS) targeting the globus pallidus internus (GPi) can improve tics and comorbid obsessive-compulsive behavior (OCB) in patients with treatment-refractory Tourette syndrome (TS). However, some patients’ symptoms remain unresponsive, the stimulation applied across patients is variable, and the mechanisms underlying improvement are unclear. Identifying the fiber pathways surrounding the GPi that are associated with improvement could provide mechanistic insight and refine targeting strategies to improve outcomes.Methods: Retrospective data were collected for 35 patients who underwent bilateral GPi DBS for TS. Computational models of fiber tract activation were constructed using patient-specific lead locations and stimulation settings to evaluate the effects of DBS on basal ganglia pathways and the internal capsule. We first evaluated the relationship between activation of individual pathways and symptom improvement. Next, linear mixed-effects models with combinations of pathways and clinical variables were compared in order to identify the best-fit predictive models of tic and OCB improvement.Results: The best-fit model of tic improvement included baseline severity and the associative pallido-subthalamic pathway. The best-fit model of OCB improvement included baseline severity and the sensorimotor pallido-subthalamic pathway, with substantial evidence also supporting the involvement of the prefrontal, motor, and premotor internal capsule pathways. The best-fit models of tic and OCB improvement predicted outcomes across the cohort and in cross-validation.Conclusions: Differences in fiber pathway activation likely contribute to variable outcomes of DBS for TS. Computational models of pathway activation could be used to develop novel approaches for preoperative targeting and selecting stimulation parameters to improve patient outcomes.
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| 18. |
- Johnson, Kara A., et al.
(author)
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Structural connectivity predicts clinical outcomes of deep brain stimulation for Tourette syndrome
- 2020
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In: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 143, s. 2607-2623
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Journal article (peer-reviewed)abstract
- Deep brain stimulation may be an effective therapy for select cases of severe, treatment-refractory Tourette syndrome; however, patient responses are variable, and there are no reliable methods to predict clinical outcomes. The objectives of this retrospective study were to identify the stimulation-dependent structural networks associated with improvements in tics and comorbid obsessive-compulsive behaviour, compare the networks across surgical targets, and determine if connectivity could be used to predict clinical outcomes. Volumes of tissue activated for a large multisite cohort of patients (n = 66) implanted bilaterally in globus pallidus internus (n = 34) or centromedial thalamus (n = 32) were used to generate probabilistic tractography to form a normative structural connectome. The tractography maps were used to identify networks that were correlated with improvement in tics or comorbid obsessive-compulsive behaviour and to predict clinical outcomes across the cohort. The correlated networks were then used to generate ‘reverse’ tractography to parcellate the total volume of stimulation across all patients to identify local regions to target or avoid. The results showed that for globus pallidus internus, connectivity to limbic networks, associative networks, caudate, thalamus, and cerebellum was positively correlated with improvement in tics; the model predicted clinical improvement scores (P = 0.003) and was robust to cross-validation. Regions near the anteromedial pallidum exhibited higher connectivity to the positively correlated networks than posteroventral pallidum, and volume of tissue activated overlap with this map was significantly correlated with tic improvement (P < 0.017). For centromedial thalamus, connectivity to sensorimotor networks, parietal-temporal-occipital networks, putamen, and cerebellum was positively correlated with tic improvement; the model predicted clinical improvement scores (P = 0.012) and was robust to cross-validation. Regions in the anterior/lateral centromedial thalamus exhibited higher connectivity to the positively correlated networks, but volume of tissue activated overlap with this map did not predict improvement (P > 0.23). For obsessive-compulsive behaviour, both targets showed that connectivity to the prefrontal cortex, orbitofrontal cortex, and cingulate cortex was positively correlated with improvement; however, only the centromedial thalamus maps predicted clinical outcomes across the cohort (P = 0.034), but the model was not robust to cross-validation. Collectively, the results demonstrate that the structural connectivity of the site of stimulation are likely important for mediating symptom improvement, and the networks involved in tic improvement may differ across surgical targets. These networks provide important insight on potential mechanisms and could be used to guide lead placement and stimulation parameter selection, as well as refine targets for neuromodulation therapies for Tourette syndrome.
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| 19. |
- Kefalopoulou, Zinovia, et al.
(author)
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Long-term clinical outcome of fetal cell transplantation for Parkinson disease : two case reports
- 2014
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In: JAMA Neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 71:1, s. 7-83
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Journal article (peer-reviewed)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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| 20. |
- Loane, Clare, et al.
(author)
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Aberrant nigral diffusion in Parkinson's disease : A longitudinal diffusion tensor imaging study
- 2016
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In: Movement Disorders. - : Wiley. - 0885-3185. ; 31:7, s. 6-1020
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Journal article (peer-reviewed)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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| 21. |
- Mahlknecht, Philipp, et al.
(author)
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Parkinsonian signs in patients with cervical dystonia treated with pallidal deep brain stimulation
- 2018
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In: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 141, s. 3023-3034
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Journal article (peer-reviewed)abstract
- Pallidal deep brain stimulation is an established treatment in patients with dystonia. However, evidence from case series or uncontrolled studies suggests that it may lead in some patients to specific parkinsonian symptoms such as freezing of gait, micrographia, and bradykinesia. We investigated parkinsonian signs using the Movement Disorder Society Unified Parkinson's Disease Rating Scale motor score by means of observer-blinded video ratings in a group of 29 patients treated with pallidal stimulation and a non-surgical control group of 22 patients, both with predominant cervical dystonia. Additional assessments included MRI-hased models of volume of neural tissue activated to investigate areas of stimulation related to dystonic symptom control and those likely to induce parkinsonian signs as well as an EMG analysis to investigate functional vicinity of stimulation fields to the pyramidal tract. Compared with controls, stimulated patients had significantly higher motor scores (median, 25th-75th percentile: 14.0, 8.0-19.5 versus 3.0, 2.0-8.0; P < 0.0001), as well as bradykinesia (8.0, 6.0-14.0 versus 2.0, 0.0-3.0; P < 0.0001) and axial motor subscores (2.0, 1.0-4.0 versus 0.0, 0.0-1.0; P= 0.0002), while rigidity and tremor subscores were not different between groups. Parkinsonian signs were partially reversible upon switching stimulation off for a median of 90 min in a subset of 19 patients tolerating this condition. Furthermore, the stimulation group reported more features of freezing of gait on a questionnaire basis. Quality of life was better in stimulated patients compared with control patients, but parkinsonian signs were negatively associated with quality of life. In the descriptive imaging analysis maximum efficacy for dystonia improvement projected to the posteroventrolateral internal pallidum with overlapping dusters driving severity of bradykinesia and axial motor symptoms. The severities of parkinsonian signs were not correlated with functional vicinity to the pyramidal tract as assessed by EMG. In conclusion, parkinsonian signs, particularly bradykinesia and axial motor signs, due to pallidal stimulation in dystonic patients are frequent and negatively impact on motor functioning and quality of life. Therefore, patients with pallidal stimulation should be monitored closely for such signs both in clinical routine and future clinical trials. Spread of current outside the internal pallidum is an unlikely explanation for this phenomenon, which seems to be caused by stimulation of neural elements within the stimulation target volume.
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| 22. |
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| 23. |
- Martinez-Fernandez, Raul, et al.
(author)
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Deep Brain Stimulation for Gilles de la Tourette Syndrome : A Case Series Targeting Subregions of the Globus Pallidus Internus
- 2011
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In: Movement Disorders. - New York, N.Y. : Raven Press. - 0885-3185 .- 1531-8257. ; 26:10, s. 1922-1930
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Journal article (peer-reviewed)abstract
- Deep brain stimulation remains an experimental treatment for patients with Gilles de la Tourette syndrome. Currently, a major controversial issue is the choice of brain target that leads to optimal patient outcomes within a presumed network of basal ganglia and cortical pathways involved in tic pathogenesis. This report describes our experience with patients with severe refractory Gilles de la Tourette syndrome treated with globus pallidus internus deep brain stimulation. Five patients were selected for surgery, 2 targeting the posteroventral globus pallidus internus and 2 targeting the anteromedial region. The remaining patient was first targeted on the posterolateral region, but after 18 months the electrodes were relocated in the anteromedial area. Tics were clinically assessed in all patients pre- and postoperatively using the Modified Rush Video protocol and the Yale Global Tic Severity Scale. Obsessive-compulsive behaviors were quantified with the Yale Brown Obsessive Compulsive Scale. The Gilles de la Tourette Syndrome Quality of Life Scale was also completed. All patients experienced improvements in tic severity but to variable extents. More convincing improvements were seen in patients with electrodes sited in the anteromedial region of the globus pallidus internus than in those with posterolateral implants. Mean reduction in the Modified Rush Video Rating scale for each group was 54% and 37%, respectively. Our open-label limited experience supports the use of the anteromedial globus pallidus internus as a promising target for future planned randomized double-blind trials of deep brain stimulation for patients with Gilles de la Tourette syndrome.
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| 24. |
- Martinez-Ramirez, Daniel, et al.
(author)
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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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In: JAMA Neurology. - : American Medical Association. - 2168-6149 .- 2168-6157. ; 75:3, s. 353-359
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Journal article (peer-reviewed)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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| 25. |
- Nakajima, Takeshi, et al.
(author)
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MRI-Guided subthalamic nucleus deep brain stimulation without microelectrode recording : can we dispense with surgery under local anaesthesia?
- 2011
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In: Stereotactic and Functional Neurosurgery. - Basel : Karger. - 1011-6125 .- 1423-0372. ; 89:5, s. 318-325
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Journal article (peer-reviewed)abstract
- Aims: Subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson's disease (PD) is traditionally performed under local anaesthetic (LA). STN visualization and routine validation of electrode location on stereotactic MRI may allow surgery under general anaesthesia (GA). This study compares the clinical outcome of MRI-guided STN DBS performed under LA or GA in a consecutive patient series. Methods: Unified Parkinson's Disease Rating Scale motor scores (UPDRS-III) in 14 GA patients (mean age 56.1 years, disease duration 13.8 years) were compared with those of 68 LA patients (mean age 57.5 years, disease duration 15.2 years). Results: Baseline UPDRS-III were worse in the GA group, both on medication (GA: 20.9 +/- 10.8; LA: 13.2 +/- 7.8, p < 0.01) and off medication (GA: 57.9 +/- 16.6; LA: 48.2 +/- 15.7, p < 0.05). On stimulation off medication motor scores significantly improved in both groups (GA: 27.3 +/- 11.8, mean 12-month follow-up; LA: 23.7 +/- 11.8, mean 14-month follow-up). The percentage improvement was similar in both groups (GA: 52.8%; LA: 50.8%, p = 0.96). Transient surgical complications occurred in 1 GA and 7 LA patients. Conclusions: MRI-guided STN DBS under GA with routine stereotactic verification of lead location did not have a negative effect on efficacy or safety. Surgery under GA is a viable option in patients who would find it hard to tolerate awake surgery due to disease severity, comorbidities or anxiety. Copyright (C) 2011 S. Karger AG, Basel
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| 26. |
- Pepper, Joshua, et al.
(author)
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Changing of the guard : reducing infection when replacing neural pacemakers
- 2017
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In: Journal of Neurosurgery. - : AMER ASSOC NEUROLOGICAL SURGEONS. - 0022-3085 .- 1933-0693. ; 126:4, s. 1165-1172
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Journal article (peer-reviewed)abstract
- OBJECTIVE Infection of deep brain stimulation (DBS) hardware has a significant impact on patient morbidity. Previous experience suggests that infection rates appear to be higher after implantable pulse generator (IPG) replacement surgery than after the de novo DBS procedure. In this study the authors examine the effect of a change in practice during DBS IPG replacements at their institution. METHODS Starting in January 2012, patient screening for methicillin-resistant Staphylococcus aureus (MRSA) and, and where necessary, eradication was performed prior to elective DBS IPG change. Moreover, topical vancomycin was placed in the IPG pocket during surgery. The authors then prospectively examined the infection rate in patients undergoing DBS IPG replacement at their center over a 3-year period with at least 9 months of follow-up. RESULTS The total incidence of infection in this prospective consecutive series of 101 IPG replacement procedures was 0%, with a mean follow-up duration of 24 +/- 11 months. This was significantly lower than the authors' previously published historical control group, prior to implementing the change in practice, where the infection rate for IPG replacement was 8.5% (8/94 procedures; p = 0.003). CONCLUSIONS This study suggests that a change in clinical practice can significantly lower infection rates in patients undergoing DBS IPG replacement. These simple measures can minimize unnecessary surgery, loss of benefit from chronic stimulation, and costly hardware replacement, further improving the cost efficacy of DBS therapies.
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| 27. |
- Pepper, Joshua, et al.
(author)
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The Risk of Hardware Infection in Deep Brain Stimulation Surgery Is Greater at Impulse Generator Replacement than at the Primary Procedure
- 2013
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In: Stereotactic and Functional Neurosurgery. - : S. Karger. - 1011-6125 .- 1423-0372. ; 91:1, s. 56-65
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Journal article (peer-reviewed)abstract
- Background/Aims: Infection of implanted hardware after deep brain stimulation (DBS) has a significant impact on patient morbidity. We examined all patients who underwent DBS procedures over the last 9 years in our centre to assess the infection rate and possible factors related to surgery that may predispose to infection. Methods: Surgical reports and clinical notes were reviewed in 273 consecutive patients who underwent a total of 519 DBS-related procedures in our institute between November 2002 and September 2011. Results:Sixteen separate hardware-related infections occurred in 11 patients. Infections occurred in 3% of all procedures and 4% of all patients. The infection rate after implantable pulse generator (IPG) replacement surgery was more than three times higher than after de novo DBS surgery. In addition, male patients were more likely to develop device-related infections. Conclusions: It is unclear why infection rates should be more than three times higher after IPG replacement surgery than after the de novo procedure. The former is a shorter and simpler procedure to conduct. Perhaps the use of better antimicrobial protection and rechargeable batteries may be useful strategies to reduce infections following IPG revision surgery.
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| 28. |
- Petersen, Erika A, et al.
(author)
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Minimizing brain shift in stereotactic functional neurosurgery
- 2010
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In: Neurosurgery. - 0148-396X .- 1524-4040. ; 67:3 Suppl, s. ons213-ons221
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Journal article (peer-reviewed)abstract
- Brain shift has long been considered an issue in stereotactic targeting during DBS procedures. However, with the image-guided approach and surgical technique used in this study, subcortical brain shift was extremely limited and did not appear to adversely affect clinical outcome.
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| 29. |
- Rajabian, Ali, et al.
(author)
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Accuracy, precision, and safety of stereotactic, frame-based, intraoperative MRI-guided and MRI-verified deep brain stimulation in 650 consecutive procedures
- 2023
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In: Journal of Neurosurgery. - : Journal of Neurosurgery Publishing Group (JNSPG). - 0022-3085 .- 1933-0693. ; 138, s. 1702-1711
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Suboptimal lead placement is one of the most common indications for deep brain stimulation (DBS) revision procedures. Confirming lead placement in relation to the visible anatomical target with dedicated stereotactic imaging before terminating the procedure can mitigate this risk. In this study, the authors examined the accuracy, precision, and safety of intraoperative MRI (iMRI) to both guide and verify lead placement during frame-based stereotactic surgery.METHODS: A retrospective analysis of 650 consecutive DBS procedures for targeting accuracy, precision, and perioperative complications was performed. Frame-based lead placement took place in an operating room equipped with an MRI machine using stereotactic images to verify lead placement before removing the stereotactic frame. Immediate lead relocation was performed when necessary. Systematic analysis of the targeting error was calculated.RESULTS: Verification of 1201 DBS leads with stereotactic MRI was performed in 643 procedures and with stereotactic CT in 7. The mean ± SD of the final targeting error was 0.9 ± 0.3 mm (range 0.1-2.3 mm). Anatomically acceptable lead placement was achieved with a single brain pass for 97% (n = 1164) of leads; immediate intraoperative relocation was performed in 37 leads (3%) to obtain satisfactory anatomical placement. General anesthesia was used in 91% (n = 593) of the procedures. Hemorrhage was noted after 4 procedures (0.6%); 3 patients (0.4% of procedures) presented with transient neurological symptoms, and 1 experienced delayed cognitive decline. Two bleeds coincided with immediate relocation (2 of 37 leads, 5.4%), which contrasts with hemorrhage in 2 (0.2%) of 1164 leads implanted on the first pass (p = 0.0058). Three patients had transient seizures in the postoperative period. The seizures coincided with hemorrhage in 2 of these patients and with immediate lead relocation in the other. There were 21 infections (3.2% of procedures, 1.5% in 3 months) leading to hardware removal. Delayed (> 3 months) retargeting of 6 leads (0.5%) in 4 patients (0.6% of procedures) was performed because of suboptimal stimulation benefit. There were no MRI-related complications, no permanent motor deficits, and no deaths.CONCLUSIONS: To the authors' knowledge, this is the largest series reporting the use of iMRI to guide and verify lead location during DBS surgery. It demonstrates a high level of accuracy, precision, and safety. Significantly higher hemorrhage was encountered when multiple brain passes were required for lead implantation, although none led to permanent deficit. Meticulous audit and calibration can improve precision and maximize safety.
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| 30. |
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| 31. |
- Roussakis, Andreas Antonios, et al.
(author)
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Parkinson’s disease laterality : a 11C-PE2I PET imaging study
- 2020
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In: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459.
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Journal article (peer-reviewed)abstract
- Asymmetry of striatal dopaminergic deficits and motor symptoms is a typical characteristic of idiopathic Parkinson’s disease (PD). This study aims to characterise the trend of asymmetry in moderate-stage PD. We performed a 19-month longitudinal study in 27 patients with PET-CT imaging and appropriate clinical assessments. 11C-PE2I non-displaceable binding potential (BPND) was calculated bilaterally for the striatum at baseline and follow-up to estimate the in vivo density of striatal dopamine transporters (DAT). Changes in striatal 11C-PE2I BPND over time were more prominent in the ipsilateral as compared to contralateral side. Changes in MDS-UPDRS-III (motor component of the Movement Disorders Society Unified PD Rating Scale) were not different between the clinically most and least affected body sides. Our data support that the asymmetry in striatal dopaminergic degeneration becomes less prominent in moderate-stage PD. In contrast, during the above period, the asymmetry of motor symptoms was maintained between the clinically most and least affected body sides.
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| 32. |
- Scott, Robert A., et al.
(author)
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A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease
- 2016
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In: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 8:341
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Journal article (peer-reviewed)abstract
- Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.
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| 33. |
- Swallow, Diane M A, et al.
(author)
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Statins are underused in recent-onset Parkinson's disease with increased vascular risk : findings from the UK Tracking Parkinson's and Oxford Parkinson's Disease Centre (OPDC) discovery cohorts
- 2016
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In: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 87:11, s. 1183-1190
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Journal article (peer-reviewed)abstract
- BACKGROUND: Cardiovascular disease (CVD) influences phenotypic variation in Parkinson's disease (PD), and is usually an indication for statin therapy. It is less clear whether cardiovascular risk factors influence PD phenotype, and if statins are prescribed appropriately.OBJECTIVES: To quantify vascular risk and statin use in recent-onset PD, and examine the relationship between vascular risk, PD severity and phenotype.METHODS: Cardiovascular risk was quantified using the QRISK2 calculator (high ≥20%, medium ≥10 and <20%, low risk <10%). Motor severity and phenotype were assessed using the Movement Disorder Society Unified PD Rating Scale (UPDRS) and cognition by the Montreal cognitive assessment.RESULTS: In 2909 individuals with recent-onset PD, the mean age was 67.5 years (SD 9.3), 63.5% were men and the mean disease duration was 1.3 years (SD 0.9). 33.8% of cases had high vascular risk, 28.7% medium risk, and 22.3% low risk, while 15.2% of cases had established CVD. Increasing vascular risk and CVD were associated with older age (p<0.001), worse motor score (p<0.001), more cognitive impairment (p<0.001) and worse motor phenotype (p=0.021). Statins were prescribed in 37.2% with high vascular risk, 15.1% with medium vascular risk and 6.5% with low vascular risk, which compared with statin usage in 75.3% of those with CVD.CONCLUSIONS: Over 60% of recent-onset PD patients have high or medium cardiovascular risk (meriting statin usage), which is associated with a worse motor and cognitive phenotype. Statins are underused in these patients, compared with those with vascular disease, which is a missed opportunity for preventive treatment.TRIAL REGISTRATION NUMBER: GN11NE062, NCT02881099.
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| 34. |
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| 35. |
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| 36. |
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| 37. |
- Zrinzo, Ludvic, et al.
(author)
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Clinical safety of brain magnetic resonance imaging with implanted deep brain stimulation hardware : large case series and review of the literature
- 2011
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In: World Neurosurgery. - New York, NY : Elsevier. - 1878-8750. ; 76:1-2, s. 164-172
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Journal article (peer-reviewed)abstract
- Background: Over 75,000 patients have undergone deep brain stimulation (DBS) procedures worldwide. Magnetic resonance imaging (MRI) is an important clinical and research tool in analyzing electrode location, documenting postoperative complications, and investigating novel symptoms in DBS patients. Functional MRI may shed light on the mechanism of action of DBS. MRI safety in DBS patients is therefore an important consideration. Methods: We report our experience with MRI in patients with implanted DBS hardware and examine the literature for clinical reports on MRI safety with implanted DBS hardware. Results: A total of 262 MRI examinations were performed in 223 patients with intracranial DBS hardware, including 45 in patients with an implanted pulse generator. Only 1 temporary adverse event occurred related to patient agitation and movement during immediate postoperative MR imaging. Agitation resolved after a few hours, and an MRI obtained before implanted pulse generator implantation revealed edema around both electrodes. Over 4000 MRI examinations in patients with implanted DBS hardware have been reported in the literature. Only 4 led to adverse events, including 2 hardware failures, 1 temporary and 1 permanent neurological deficit. Adverse neurological events occurred in a unique set of circumstances where appropriate safety protocols were not followed. MRI guidelines provided by DBS hardware manufacturers are inconsistent and vary among devices. Conclusions: The importance of MRI in modern medicine places pressure on industry to develop fully MRI-compatible DBS devices. Until then, the literature suggests that, when observing certain precautions, cranial MR images can be obtained with an extremely low risk in patients with implanted DBS hardware.
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| 38. |
- Zrinzo, Ludvic, et al.
(author)
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Deep brain stimulation and hemorrhage RESPONSE
- 2012
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In: Journal of Neurosurgery. - Rolling Meadows : American Association of Neurological Surgeons. - 0022-3085 .- 1933-0693. ; 116:4, s. 930-932
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Journal article (peer-reviewed)
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| 39. |
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| 40. |
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| 41. |
- Zrinzo, Ludvic, et al.
(author)
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Reducing hemorrhagic complications in functional neurosurgery : a large case series and systematic literature review Clinical article
- 2012
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In: Journal of Neurosurgery. - 0022-3085 .- 1933-0693. ; 116:1, s. 84-94
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Research review (peer-reviewed)abstract
- Object. Hemorrhagic complications carry by far the highest risk of devastating neurological outcome in functional neurosurgery. Literature published over the past 10 years suggests that hemorrhage, although relatively rare, remains a significant problem. Estimating the true incidence of and risk factors for hemorrhage in functional neurosurgery is a challenging issue. Methods. The authors analyzed the hemorrhage rate in a consecutive series of 214 patients undergoing image-guided deep brain stimulation (DBS) lead placement without microelectrode recording (MER) and with routine postoperative MR imaging lead verification. They also conducted a systematic review of the literature on stereotactic ablative surgery and DBS over a 10-year period to determine the incidence and risk factors for hemorrhage as a complication of functional neurosurgery. Results. The total incidence of hemorrhage in our series of image-guided DBS was 0.9%: asymptomatic in 0.5%, symptomatic in 0.5%, and causing permanent deficit in 0.0% of patients. Weighted means calculated from the literature review suggest that the overall incidence of hemorrhage in functional neurosurgery is 5.0%, with asymptomatic hemorrhage occurring in 1.9% of patients, symptomatic hemorrhage in 2.1% and hemorrhage resulting in permanent deficit or death in 1.1%. Hypertension and age were the most important patient-related factors associated with an increased risk of hemorrhage. Risk factors related to surgical technique included use of MER, number of MER penetrations, as well as sulcal or ventricular involvement by the trajectory. The incidence of hemorrhage in studies adopting an image-guided and image-verified approach without MER was significantly lower than that reported with other operative techniques (p < 0.001 for total number of hemorrhages, p < 0.001 for asymptomatic hemorrhage, p < 0.004 for symptomatic hemorrhage, and p = 0.001 for hemorrhage leading to permanent deficit; Fisher exact test). Conclusions. Age and a history of hypertension are associated with an increased risk of hemorrhage in functional neurosurgery. Surgical factors that increase the risk of hemorrhage include the use of MER and sulcal or ventricular incursion. The meticulous use of neuroimaging-both in planning the trajectory and for target verification-can avoid all of these surgery-related risk factors and appears to carry a significantly lower risk of hemorrhage and associated permanent deficit. (DOI: 10.3171/2011.8.JNS101407)
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| 42. |
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