| 1. |
- Akram, Harith, et al.
(författare)
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Connectivity derived thalamic segmentation in deep brain stimulation for tremor
- 2018
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Ingår i: NeuroImage. - : Elsevier. - 2213-1582. ; 18, s. 130-142
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Tidskriftsartikel (refereegranskat)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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| 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. |
- Dayal, Viswas, et al.
(författare)
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Pedunculopontine nucleus deep brain stimulation for parkinsonian disorders : a case series
- 2021
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Ingår i: Stereotactic and Functional Neurosurgery. - : S. Karger. - 1011-6125 .- 1423-0372. ; 99:4, s. 287-294
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Dayal, Viswas, et al.
(författare)
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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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Ingår i: Movement Disorders. - : John Wiley & Sons. - 0885-3185 .- 1531-8257. ; 35:1, s. 101-108
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Tidskriftsartikel (refereegranskat)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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| 6. |
- Wirth, Thomas, et al.
(författare)
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Clinical outcomes after MRI connectivity-guided radiofrequency thalamotomy for tremor
- 2024
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Ingår i: Journal of Neurosurgery. - : American Association of Neurological Surgeons. - 0022-3085 .- 1933-0693. ; 140:4, s. 1148-1154
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Tidskriftsartikel (refereegranskat)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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