| 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. |
- Akram, Harith, et al.
(författare)
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Aim for the Suprasternal Notch : Technical Note to Avoid Bowstringing after Deep Brain Stimulation
- 2015
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Ingår i: Stereotactic and Functional Neurosurgery. - : S. Karger AG. - 1011-6125 .- 1423-0372. ; 93:4, s. 227-230
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Tidskriftsartikel (refereegranskat)abstract
- Background: Bowstringing may occur when excessive fibrosis develops around extension cables in the neck after deep brain stimulation (DBS) surgery. Though the occurrence of this phenomenon is rare, we have noted that it tends to cause maximal discomfort when the cables cross superficially over the convexity of the clavicle. We hypothesise that bowstringing may be avoided by directing the extension cables towards the suprasternal notch. Methods: When connecting DBS leads to an infraclavicular pectoral implantable pulse generator (IPG), tunnelling is directed towards the suprasternal I notch, before being directed laterally towards the IPG pocket. In previously operated patients with established fibrosis, the fibrous tunnel is opened and excised as far cranially as possible, allowing medial rerouting of cables. Using this approach, we reviewed our series of patients who underwent DBS surgery over 10 years. Results: In 429 patients, 7 patients (2%) with cables tunnelled over the convexity of the clavicle complaining of bowstringing underwent cable exploration and rerouting. This eliminated bowstringing and provided better cosmetic results. When the cable trajectory was initially directed towards the suprasternal notch, no bowstringing was observed. Conclusion:The tunnelling trajectory appears to influence postoperative incidence of fibrosis associated with DBS cables. Modifying the surgical technique may reduce the incidence of this troublesome adverse event. (C) 2015 S.Karger AG, Basel
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| 3. |
- 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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| 4. |
- Akram, Harith, et al.
(författare)
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L-Dopa Responsiveness Is Associated With Distinctive Connectivity Patterns in Advanced Parkinson's Disease
- 2017
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Ingår i: Movement Disorders. - : Wiley-Blackwell. - 0885-3185 .- 1531-8257. ; 32:6, s. 874-883
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Subthalamic deep brain stimulation sweet spots and hyperdirect cortical connectivity in Parkinson's disease
- 2017
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Ingår i: NeuroImage. - : Elsevier. - 1053-8119 .- 1095-9572. ; 158, s. 332-345
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Tidskriftsartikel (refereegranskat)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. |
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| 7. |
- Cappon, Davide, et al.
(författare)
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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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Ingår i: Movement Disorders Clinical Practice. - : John Wiley & Sons. - 2330-1619. ; 9:6, s. 765-774
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Tidskriftsartikel (refereegranskat)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.
(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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| 9. |
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| 10. |
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| 11. |
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| 12. |
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| 13. |
- Cif, Laura, et al.
(författare)
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The Influence of Deep Brain Stimulation Intensity and Duration on Symptoms Evolution in an OFF Stimulation Dystonia Study
- 2013
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Ingår i: Brain stimulation. - : Elsevier BV. - 1935-861X. ; 6:4, s. 500-505
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Tidskriftsartikel (refereegranskat)abstract
- Background: Deep brain stimulation (DBS) of the internal globus pallidus (GPi) is an established therapy for primary generalized dystonia. However, the evolution of dystonia symptoms after DBS discontinuation after years of therapy has only rarely been reported. We therefore longitudinally studied the main physiological measurements known to be impaired in dystonia, with DBS ON and then again after termination of DBS, after at least five years of continuous DBS. Objective: We studied whether dystonia evolution after DBS discontinuation in patients benefiting from long-term GPi DBS is different from that observed in earlier stages of the therapy. Methods: In eleven DYT1 patients treated with bilateral GPi DBS for at least 5 years, dystonia was assessed ON-DBS, immediately after switch-off (OFF-DBS1) and 48 h after DBS termination (OFF-DBS2). We studied the influence of DBS intensity on dystonia when DBS was discontinued. Results: On average a significant difference in symptoms was measured only between ON-DBS and OFF-DBS1 conditions. Importantly, none of the patients returned to their preoperative dystonia severity, even 48 h after discontinuation. The amount of clinical deterioration in the OFF conditions positively correlated with higher stimulation current in the chronic ON-DBS condition. Conclusions: The duration of DBS application influences symptom evolution after DBS termination. DBS intensity seems to have a prominent role on evolution of dystonic symptoms when DBS is discontinued. In conclusion, DBS induces changing modulation of the motor network with less worsening of symptoms after long term stimulation, when DBS is stopped.
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| 14. |
- 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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| 15. |
- 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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| 16. |
- Eusebio, Alexandre, et al.
(författare)
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Effects of low-frequency stimulation of the subthalamic nucleus on movement in Parkinson's disease.
- 2008
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886 .- 1090-2430. ; 209:1, s. 125-30
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Tidskriftsartikel (refereegranskat)abstract
- Excessive synchronization of basal ganglia neural activity at low frequencies is considered a hallmark of Parkinson's disease (PD). However, few studies have unambiguously linked this activity to movement impairment through direct stimulation of basal ganglia targets at low frequency. Furthermore, these studies have varied in their methodology and findings, so it remains unclear whether stimulation at any or all frequencies < or = 20 Hz impairs movement and if so, whether effects are identical across this broad frequency band. To address these issues, 18 PD patients chronically implanted with deep brain stimulation (DBS) electrodes in both subthalamic nuclei were stimulated bilaterally at 5, 10 and 20 Hz after overnight withdrawal of their medication and the effects of the DBS on a finger tapping task were compared to performance without DBS (0 Hz). Tapping rate decreased at 5 and 20 Hz compared to 0 Hz (by 11.8+/-4.9%, p=0.022 and 7.4+/-2.6%, p=0.009, respectively) on those sides with relatively preserved baseline task performance. Moreover, the coefficient of variation of tap intervals increased at 5 and 10 Hz compared to 0 Hz (by 70.4+/-35.8%, p=0.038 and 81.5+/-48.2%, p=0.043, respectively). These data suggest that the susceptibility of basal ganglia networks to the effects of excessive synchronization may be elevated across a broad low-frequency band in parkinsonian patients, although the nature of the consequent motor impairment may depend on the precise frequencies at which synchronization occurs.
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| 17. |
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| 18. |
- Hariz, Gun-Marie, et al.
(författare)
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"DBS means everything - for some time" : Patients' Perspectives on Daily Life with Deep Brain Stimulation for Parkinson's Disease
- 2016
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Ingår i: Journal of Parkinson's Disease. - 1877-7171 .- 1877-718X. ; 6:2, s. 335-347
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Tidskriftsartikel (refereegranskat)abstract
- Background: Deep brain stimulation (DBS) is an established treatment for Parkinson's disease. However, patients' own perceptions of the impact of DBS on their daily living is not fully explored. Objective: We aimed to collect and analyse patients' narratives about their everyday experiences of being on chronic DBS. Methods: Semi-structured interviews with open-ended questions were conducted with 42 patients (11 women) who had been on DBS for a mean of three years. The questions were related to patients' ordinary daily life and eventual changes, both negative and positive, brought about by DBS. The interviews were transcribed verbatim and analysed according to the difference and similarity technique in grounded theory. Results: From the patients' narratives the core category `DBS means everything - for some time' was established, and supported by the following categories: 1) Relief from invasive tremor. 2) A rescue from cramps and pain. 3) Easier movement swings and more predictable living space. 4) Hard, but compared to previous suffering, bearable adverse events. 5) Parkinson's disease is progressing despite DBS. Conclusions: The analysis of the participants' narratives shed light on patients' unique perceptions and perspectives of the impact of DBS on their everyday lives. Patients with advanced PD highly appreciated the positive impact of DBS on their daily life even if this impact is limited in time. For the majority, the relief from the severe parkinsonian symptoms, especially tremor and painful cramps, outweighed the side effects of DBS. The study provided information not readily captured by pre-formulated questionnaires and scales.
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| 19. |
- Hariz, Gun-Marie, 1954-, et al.
(författare)
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Gender distribution of patients with Parkinson's disease treated with subthalamic deep brain stimulation : a review of the 2000-2009 literature
- 2011
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier. - 1353-8020 .- 1873-5126. ; 17:3, s. 146-149
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Forskningsöversikt (refereegranskat)abstract
- Purpose: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been the mainstream surgical procedure for advanced Parkinson’s disease (PD) during the last decade. Reports from a few individual centres have hinted that women who receive STN DBS are under-represented. We aimed to evaluate the gender distribution of patients with PD who had received STN DBS during the last ten years, and to discuss the findings in relation to studies on gender prevalence of PD.Methods: A search of the PubMed database of clinical papers in English language related to STN DBS between 2000 and 2009 was conducted. Care was taken to minimize redundancies in reporting of published patients. The proportion of men and women were expressed in total and according to pre-defined geographic regions.Results: One hundred and thirty five papers were eligible for review. The gender of the patients was specified in 119 papers on a total of 3880 patients, of which 63% were men. According to geographic origin of publications, the percentage of men with STN DBS was 68% in North America, 62% in Europe, 69% in Australia and 50% in Asia.Conclusions: The proportion of male patients who undergo STN DBS seems to exceed the reported male/female ratio of patients with PD.
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| 20. |
- Hariz, Gun-Marie, et al.
(författare)
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Patients' perceptions of life shift after deep brain stimulation for primary dystonia : a qualitative study
- 2011
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 26:11, s. 2101-2106
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Tidskriftsartikel (refereegranskat)abstract
- Studies of deep brain stimulation for dystonia have shown significant motor improvement. However, patients' perceptions of surgery and its effects have been less studied. We aimed to explore perceptions of changes in life in patients with primary dystonia after deep brain stimulation. Thirteen patients underwent thematic interviews 8-60 months after pallidal deep brain stimulation. Interviews were transcribed verbatim and analyzed with grounded theory. Patients described a profound impact of dystonia on daily life. After surgery, physical changes with a more upright posture and fewer spasms translated into an easier, more satisfying life with greater confidence. Notwithstanding this positive outcome, the transition from a limited life before surgery to opportunities for a better life exhibited obstacles: The "new life" after deep brain stimulation was stressful, including concern about being dependent on the stimulator as well as having to deal with interfering side effects from deep brain stimulation. The whole coping process meant that patients had to quickly shift focus from struggling to adapt to a slowly progressive disorder to adjustment to a life with possibilities, but also with new challenges. In this demanding transition process, patients wished to be offered better professional guidance and support. Even though deep brain stimulation provides people with primary dystonia with a potential for better mobility and more confidence, patients experienced new challenges and expressed the need for support and counseling after surgery. Grounded theory is a useful method to highlight patients' own experience and contributes to a deeper understanding of the impact of deep brain stimulation on patients with dystonia.
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| 21. |
- Hariz, Gun-Marie, et al.
(författare)
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Women pioneers in basal ganglia surgery
- 2014
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier BV. - 1873-5126 .- 1353-8020. ; 20:2, s. 137-141
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Forskningsöversikt (refereegranskat)abstract
- Background: Stereotactic functional neurosurgery on basal ganglia has a long history and the pioneers are mostly men. We aimed at finding out if there were women who have contributed pioneering work in this field. Methods: The literature was searched to identify women who have been first to publish innovative papers related to human basal ganglia surgery. Results: Six women fulfilling our criteria were found: Marion Smith, a British neuropathologist, made unique observations on stereotactic lesions of basal ganglia and thalamus on autopsied brains, and the lesions' relation to the reported clinical outcome. Natalia Bechtereva, a Russian neurophysiologist, pioneered the technique of therapeutic chronic deep brain stimulation to treat various brain disorders, including Parkinson's disease (PD). Denise Albe-Fessard, a French neurophysiologist, pioneered the technique of microelectrode recording (MER) in stereotactic functional neurosurgery. Gunvor Kullberg, a Swedish neurosurgeon, contributed in early CT imaging as well as early functional imaging of stereotactic lesions in PD and psychiatric patients. Hilda Molina, a Cuban neurosurgeon, established the Centro Internacional de Restauracion Neurologica (CIREN) and pioneered there MER-guided transplant surgery in PD patients. Veerle Vandewalle, a Belgian neurosurgeon, pioneered in 1999 deep brain stimulation (DBS) for Tourette Syndrome. Conclusion: Although men constitute the great majority of neurosurgeons, neurologists and other neuro-specialists who have made groundbreaking contributions in basal ganglia surgery, there are women who have made equally important and unique contributions to the field. The principal two techniques used today in functional stereotactic neurosurgery, MER and DBS, have once upon a time been pioneered by women. (C) 2013 Elsevier Ltd. All rights reserved.
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| 22. |
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| 23. |
- Holl, Etienne M, et al.
(författare)
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Improving targeting in image-guided frame-based deep brain stimulation
- 2010
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Ingår i: Neurosurgery. - 0148-396X .- 1524-4040. ; 67:2 Suppl, s. ons437-ons447
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Tidskriftsartikel (refereegranskat)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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| 24. |
- Hyam, Jonathan A, et al.
(författare)
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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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Ingår i: Operative Neurosurgery. - : Lippincott Williams & Wilkins. - 2332-4252 .- 2332-4260. ; 11:3, s. 412-419
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Tidskriftsartikel (refereegranskat)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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| 25. |
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| 26. |
- 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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| 27. |
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| 28. |
- Mahlknecht, Philipp, et al.
(författare)
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Parkinsonian signs in patients with cervical dystonia treated with pallidal deep brain stimulation
- 2018
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Ingår i: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 141, s. 3023-3034
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Tidskriftsartikel (refereegranskat)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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| 29. |
- Martinez-Fernandez, Raul, et al.
(författare)
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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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Ingår i: Movement Disorders. - New York, N.Y. : Raven Press. - 0885-3185 .- 1531-8257. ; 26:10, s. 1922-1930
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Tidskriftsartikel (refereegranskat)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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| 30. |
- Meyer, Esther, et al.
(författare)
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Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia.
- 2017
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 49, s. 223-237
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Tidskriftsartikel (refereegranskat)abstract
- Histone lysine methylation, mediated by mixed-lineage leukemia (MLL) proteins, is now known to be critical in the regulation of gene expression, genomic stability, cell cycle and nuclear architecture. Despite MLL proteins being postulated as essential for normal development, little is known about the specific functions of the different MLL lysine methyltransferases. Here we report heterozygous variants in the gene KMT2B (also known as MLL4) in 27 unrelated individuals with a complex progressive childhood-onset dystonia, often associated with a typical facial appearance and characteristic brain magnetic resonance imaging findings. Over time, the majority of affected individuals developed prominent cervical, cranial and laryngeal dystonia. Marked clinical benefit, including the restoration of independent ambulation in some cases, was observed following deep brain stimulation (DBS). These findings highlight a clinically recognizable and potentially treatable form of genetic dystonia, demonstrating the crucial role of KMT2B in the physiological control of voluntary movement.
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| 31. |
- Mullin, Stephen, et al.
(författare)
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Ambroxol for the Treatment of Patients With Parkinson Disease With and Without Glucocerebrosidase Gene Mutations: A Nonrandomized, Noncontrolled Trial.
- 2020
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 77:4, s. 427-34
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Tidskriftsartikel (refereegranskat)abstract
- Mutations of the glucocerebrosidase gene, GBA1 (OMIM 606463), are the most important risk factor for Parkinson disease (PD). In vitro and in vivo studies have reported that ambroxol increases β-glucocerebrosidase (GCase) enzyme activity and reduces α-synuclein levels. These observations support a potential role for ambroxol therapy in modifying a relevant pathogenetic pathway in PD.To assess safety, tolerability, cerebrospinal fluid (CSF) penetration, and target engagement of ambroxol therapy with GCase in patients with PD with and without GBA1 mutations.An escalating dose of oral ambroxol to 1.26 g per day.This single-center open-label noncontrolled clinical trial was conducted between January 11, 2017, and April 25, 2018, at the Leonard Wolfson Experimental Neuroscience Centre, a dedicated clinical research facility and part of the University College London Queen Square Institute of Neurology in London, United Kingdom. Participants were recruited from established databases at the Royal Free London Hospital and National Hospital for Neurology and Neurosurgery in London. Twenty-four patients with moderate PD were evaluated for eligibility, and 23 entered the study. Of those, 18 patients completed the study; 1 patient was excluded (failed lumbar puncture), and 4 patients withdrew (predominantly lumbar puncture-related complications). All data analyses were performed from November 1 to December 14, 2018.Primary outcomes at 186 days were the detection of ambroxol in the CSF and a change in CSF GCase activity.Of the 18 participants (15 men [83.3%]; mean [SD] age, 60.2 [9.7] years) who completed the study, 17 (8 with GBA1 mutations and 9 without GBA1 mutations) were included in the primary analysis. Between days 0 and 186, a 156-ng/mL increase in the level of ambroxol in CSF (lower 95% confidence limit, 129 ng/mL; P<.001) was observed. The CSF GCase activity decreased by 19% (0.059 nmol/mL per hour; 95% CI, -0.115 to -0.002; P=.04). The ambroxol therapy was well tolerated, with no serious adverse events. An increase of 50 pg/mL (13%) in the CSF α-synuclein concentration (95% CI, 14-87; P=.01) and an increase of 88 ng/mol (35%) in the CSF GCase protein levels (95% CI, 40-137; P=.002) were observed. Mean (SD) scores on part 3 of the Movement Disorders Society Unified Parkinson Disease Rating Scale decreased (ie, improved) by 6.8 (7.1) points (95% CI, -10.4 to -3.1; P=.001). These changes were observed in patients with and without GBA1 mutations.The study results suggest that ambroxol therapy was safe and well tolerated; CSF penetration and target engagement of ambroxol were achieved, and CSF α-synuclein levels were increased. Placebo-controlled clinical trials are needed to examine whether ambroxol therapy is associated with changes in the natural progression of PD.ClinicalTrials.gov identifier: NCT02941822; EudraCT identifier: 2015-002571-24.
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| 32. |
- Nakajima, Takeshi, et al.
(författare)
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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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Ingår i: Stereotactic and Functional Neurosurgery. - Basel : Karger. - 1011-6125 .- 1423-0372. ; 89:5, s. 318-325
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Tidskriftsartikel (refereegranskat)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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| 33. |
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| 34. |
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| 35. |
- Pepper, Joshua, et al.
(författare)
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Changing of the guard : reducing infection when replacing neural pacemakers
- 2017
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Ingår i: Journal of Neurosurgery. - : AMER ASSOC NEUROLOGICAL SURGEONS. - 0022-3085 .- 1933-0693. ; 126:4, s. 1165-1172
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Tidskriftsartikel (refereegranskat)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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| 36. |
- Pepper, Joshua, et al.
(författare)
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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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Ingår i: Stereotactic and Functional Neurosurgery. - : S. Karger. - 1011-6125 .- 1423-0372. ; 91:1, s. 56-65
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Tidskriftsartikel (refereegranskat)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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| 37. |
- Petersen, Erika A, et al.
(författare)
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Minimizing brain shift in stereotactic functional neurosurgery
- 2010
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Ingår i: Neurosurgery. - 0148-396X .- 1524-4040. ; 67:3 Suppl, s. ons213-ons221
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Tidskriftsartikel (refereegranskat)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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| 38. |
- Rajabian, Ali, et al.
(författare)
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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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Ingår i: Journal of Neurosurgery. - : Journal of Neurosurgery Publishing Group (JNSPG). - 0022-3085 .- 1933-0693. ; 138, s. 1702-1711
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Tidskriftsartikel (refereegranskat)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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| 39. |
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| 40. |
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| 41. |
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| 42. |
- Tisch, Stephen, et al.
(författare)
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Cortical evoked potentials from pallidal stimulation in patients with primary generalized dystonia.
- 2008
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Ingår i: Movement disorders : official journal of the Movement Disorder Society. - : Wiley. - 1531-8257. ; 23:2, s. 265-73
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Tidskriftsartikel (refereegranskat)abstract
- Deep brain stimulation (DBS) of globus pallidus internus (GPi) has emerged as an effective treatment for primary generalized dystonia. However, the physiological mechanisms of improvement are not fully understood. Cortical activity in response to pallidal stimulation was recorded in 6 patients with primary generalized dystonia >6 months after bilateral GPi DBS. Scalp electroencephalogram was recorded using 60 surface electrodes during 10 Hz bipolar pallidal DBS at each electrode contact pair. Anatomical position of the electrode contacts in relation to the GPi, medial medullary lamina and globus pallidus externus (GPe) was determined from the postoperative stereotactic MRI. In all six patients an evoked potential (EP) was observed with average onset latency of 10.9 ms +/- 0.77, peak latency 26.6 ms +/- 1.6, distributed mainly over the ipsilateral hemisphere, maximal centrally. The mean amplitude of this potential was larger with stimulation in posteroventral GPi than in GPe (3.36 microV vs. 0.50 microV, P < 0.0001). The EP was absent in one patient-side, ipsilateral to a previous thalamotomy. Low frequency GPi stimulation produces an EP distributed centrally over the ipsilateral hemisphere. The latency and distribution of the EP are consistent with stimulation of pallidothalamic neurons projecting to the sensorimotor cortex. Because the EP is larger and more consistently present with stimulation of posteroventral GPi than GPe, it may provide a physiological tool to identify contacts within the optimal surgical target.
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| 43. |
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| 44. |
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| 45. |
- Tripoliti, Elina, et al.
(författare)
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Effects of contact location and voltage amplitude on speech and movement in bilateral subthalamic nucleus deep brain stimulation.
- 2008
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Ingår i: Movement disorders : official journal of the Movement Disorder Society. - : Wiley. - 1531-8257. ; 23:16, s. 2377-83
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Tidskriftsartikel (refereegranskat)abstract
- Subthalamic nucleus deep brain stimulation (STN-DBS) is particularly effective in improving limb symptoms in Parkinson's disease. However, speech shows a variable response. Contact site and amplitude of stimulation have been suggested as possible factors influencing speech. In this double blind study, we assessed 14 patients post bilateral STN-DBS, without medication. Six conditions were studied in random order as follows: stimulation inside the STN at low voltage (2 V) and at high voltage (4 V); above the STN at 2 V and at 4 V, at usual clinical parameters, and off-stimulation. The site of stimulation was defined on the postoperative stereotactic MRI data. Speech protocol consisted of the assessment of intelligibility of the dysarthric speech, maximum sustained phonation, and a 1-minute monologue. Movement was assessed using the UPDRS-III. Stimulation at 4 V significantly reduced the speech intelligibility (P = 0.004) independently from the site of stimulation. Stimulation at 4 V significantly improved the motor function. Stimulation inside the nucleus was significantly more effective than outside the nucleus (P = 0.0006). The significant improvement in movement coupled with significant deterioration in speech intelligibility when patients are stimulated inside the nucleus at high voltage indicates a critical role for electrical stimulation parameters in speech motor control.
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| 46. |
- Tyagi, Himanshu, et al.
(författare)
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A randomized trial directly comparing ventral capsule and anteromedial subthalamic nucleus stimulation in obsessive-compulsive disorder : Clinical and imaging evidence for dissociable effects
- 2022
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Ingår i: FOCUS. - : American Psychiatric Association Publishing. - 1541-4094 .- 1541-4108. ; 20:1, s. 160-169
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Tidskriftsartikel (refereegranskat)abstract
- Background: Deep brain stimulation (DBS) is an emerging treatment for severe obsessive-compulsive disorder (OCD). We compared the efficacy of ventral capsule/ventral striatal (VC/VS) and anteromedial subthalamic nucleus (amSTN) DBS in the same patients and tested for mechanistic differences on mood and cognitive flexibility and associated neural circuitry. The possible synergistic benefit of DBS at both sites and cognitive behavioral therapy was explored.Methods: Six patients with treatment-refractory OCD (5 men; Yale-Brown Obsessive Compulsive Scale score >32) entered double-blind counterbalanced phases of 12-week amSTN or VC/VS DBS, followed by 12-week open phases when amSTN and VC/VS were stimulated together, in which optimal stimulation parameters were achieved and adjunctive inpatient cognitive behavioral therapy was delivered. OCD and mood were assessed with standardized scales and cognitive flexibility with the Cambridge Neuropsychological Test Automated Battery Intra-Extra Dimensional Set-Shift task. Diffusion-weighted and intraoperative magnetic resonance imaging scans were performed for tractography from optimally activated electrode contacts.Results: DBS at each site significantly and equivalently reduced OCD symptoms with little additional gain following combined stimulation. amSTN but not VC/VS DBS significantly improved cognitive flexibility, whereas VC/VS DBS had a greater effect on mood. The VC/VS effective site was within the VC. VC DBS connected primarily to the medial orbitofrontal cortex, and amSTN DBS to the lateral orbitofrontal cortex, dorsal anterior cingulate cortex, and dorsolateral prefrontal cortex. No further improvement followed cognitive behavioral therapy, reflecting a floor effect of DBS on OCD.Conclusions: Both the VC/VS and amSTN are effective targets for severe treatment-refractory OCD. Differential improvements in mood and cognitive flexibility and their associated connectivity suggest that DBS at these sites modulates distinct brain networks.
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| 47. |
- 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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| 48. |
- Wirth, Thomas, et al.
(författare)
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Parkinson's disease tremor differentially responds to levodopa and subthalamic stimulation
- 2023
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Ingår i: Movement Disorders Clinical Practice. - : John Wiley & Sons. - 2330-1619. ; 10:11, s. 1639-1649
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Tidskriftsartikel (refereegranskat)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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| 49. |
- Wårdell, Karin, et al.
(författare)
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Deep Brain Stimulation of the Pallidum Internum for Gilles de la Tourette Syndrome : A Patient-Specific Model-Based Simulation Study of the Electric Field
- 2015
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Ingår i: Neuromodulation. - : John Wiley & Sons. - 1094-7159 .- 1525-1403. ; :2, s. 90-96
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesThe aim of this study was to investigate the deep brain stimulation (DBS) electric field distribution in proton-density MRI scans visualizing the globus pallidus internus (GPi) of patients with Gilles de la Tourette syndrome (GTS), along with its relation to the anatomy.MethodsPatient-specific brain tissue models (n = 7) with bilateral DBS electrodes in the GPi were set up using the finite element method in five patients who had undergone stereotactic proton-density MRI-guided surgery and showed variable improvement with DBS. Simulations (n = 27) of the electric field were performed and the results visualized on the respective preoperative stereotactic MRI scans. The mean electric field volumes (n = 81) within the 0.1, 0.15, and 0.2 V/mm isosurfaces were calculated and compared with the anatomy.ResultsVisualization of the simulated electric field confirmed that the anteromedial limbic GPi was the main stimulated target for four of the patients and the posteromedial sensorimotor GPi for one. Larger volumes extended asymmetrically, with parts of fields stretching into the lamina between GPi and globus pallidus externus and into the internal capsule. There was a high correlation (r = 0.994, n = 54) between volumes and brain sides, but with a systematic shift toward the right side, especially for the larger volumes. Simulations with homogeneous tissue models showed no differences.ConclusionsPatient-specific DBS electric field simulations in the GPi as visualized on proton-density MR scans can be implemented in patients with GTS. Visualization of electric fields together with stereotactic thin-slice MRI can provide further support when predicting anatomical structures possibly influenced by DBS in this complex disorder.
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