| 1. |
- 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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| 2. |
- 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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| 3. |
- Delalić, Sentilija, et al.
(author)
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Parkinson's disease in a patient with multiple sclerosis and heterozygous glucocerebrosidase gene mutation
- 2020
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In: Clinical Parkinsonism and Related Disorders. - : Elsevier. - 2590-1125. ; 3
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Journal article (peer-reviewed)abstract
- More than 30 patients with multiple sclerosis (MS) and Parkinson's disease (PD) have been reported so far. Theories on the co-occurrence of MS and PD range from coincidental to causal. There has been only one report of MS in young onset PD in a patient heterozygous for Parkin mutation. We report a patient with MS who developed signs typical for PD and was found to be heterozygous mutation carrier in the gene for glucocerebrosidase (GBA1), a well-known risk factor for PD.
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| 4. |
- Georgiev, Dejan, et al.
(author)
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Gender differences in Parkinson's disease : a clinical perspective
- 2017
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In: Acta Neurologica Scandinavica. - : John Wiley & Sons. - 0001-6314 .- 1600-0404. ; 136:6, s. 570-584
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Journal article (peer-reviewed)abstract
- Available data indicate that there are gender differences in many features of Parkinson's disease (PD). Precise identification of the gender differences is important to tailor treatment, predict outcomes, and meet other individual and social needs in women and men with PD. The aim of this study was to review the available clinical data on gender differences in PD. Original articles and meta-analyses published between 1990 and 2016 systematically exploring gender differences in PD were reviewed. There is slight male preponderance in incidence and prevalence of PD. PD starts earlier in men. Women tend to be more prone to develop tremor-dominant PD but are less rigid than men. Motor improvement after deep brain stimulation is equal in both sexes, but women tend to show better improvement in activities of daily living. Furthermore, women with PD show better results on tests for general cognitive abilities, outperform men in verbal cognitive tasks, show more pain symptoms, and score higher on depression scales. It seems, however, that the differences in cognition, mood, and pain perception are not disease specific as similar gender differences can be found in healthy subjects and in other neurological conditions. Despite PD being the most frequently studied movement disorder, studies investigating gender differences in PD are still scarce with most of the studies being cross-sectional. Good-quality, prospective, longitudinal studies analyzing gender differences in PD and comparing them to matched healthy controls are needed in order to properly address the issues of gender differences in PD.
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| 5. |
- 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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| 6. |
- Sadikov, Aleksander, et al.
(author)
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Feasibility of spirography features for objective assessment of motor function in Parkinson's disease
- 2017
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In: Artificial Intelligence in Medicine. - : Elsevier BV. - 0933-3657 .- 1873-2860. ; 81:SI, s. 54-62
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Journal article (peer-reviewed)abstract
- Objective: Parkinson's disease (PD) is currently incurable, however proper treatment can ease the symptoms and significantly improve the quality of life of patients. Since PD is a chronic disease, its efficient monitoring and management is very important. The objective of this paper was to investigate the feasibility of using the features and methodology of a spirography application, originally designed to detect early Parkinson's disease (PD) motoric symptoms, for automatically assessing motor symptoms of advanced PD patients experiencing motor fluctuations. More specifically, the aim was to objectively assess motor symptoms related to bradykinesias (slowness of movements occurring as a result of under-medication) and dyskinesias (involuntary movements occurring as a result of over-medication).Materials and methods: This work combined spirography data and clinical assessments from a longitudinal clinical study in Sweden with the features and pre-processing methodology of a Slovenian spirography application. The study involved 65 advanced PD patients and over 30,000 spiral-drawing measurements over the course of three years. Machine learning methods were used to learn to predict the "cause" (bradykinesia or dyskinesia) of upper limb motor dysfunctions as assessed by a clinician who observed animated spirals in a web interface. The classification model was also tested for comprehensibility. For this purpose a visualisation technique was used to present visual clues to clinicians as to which parts of the spiral drawing (or its animation) are important for the given classification.Results: Using the machine learning methods with feature descriptions and pre-processing from the Slovenian application resulted in 86% classification accuracy and over 0.90 AUC. The clinicians also rated the computer's visual explanations of its classifications as at least meaningful if not necessarily helpful in over 90% of the cases.Conclusions: The relatively high classification accuracy and AUC demonstrates the usefulness of this approach for objective monitoring of PD patients. The positive evaluation of computer's explanations suggests the potential use of this methodology in a decision support setting.
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| 7. |
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| 8. |
- Sperens, Maria, et al.
(author)
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Activities of daily living in Parkinson's disease : Time/gender perspective
- 2020
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In: Acta Neurologica Scandinavica. - : John Wiley & Sons. - 0001-6314 .- 1600-0404. ; 141:2, s. 168-176
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Journal article (peer-reviewed)abstract
- Objective: The objectives of this study were to explore the changes in the activities of daily living (ADL) in persons with Parkinson's disease (pwPD) over time and to investigate possible differences in ADL performance between men and women with PD.Materials & Methods: One hundred twenty‐nine persons (76 men) with a clinically established PD self‐assessed their ADL performance from the time of diagnosis up to 8 years follow‐up using the ADL taxonomy. Other demographic and clinical data (motor state, cognition, depression) were also collected and subjected to further analysis.Results: Nine of 12 domains in the ADL taxonomy showed a change over time (Eating and Drinking [P = .009], Mobility [P < .001], Toilet activities [P = .031], Dressing [P < .001], Personal hygiene [P < .001], Communication [P < .001], Cooking [P = .001], Shopping [P < .001] and Cleaning [P < .001]). In addition to time, two domains, (Shopping [P = .007] and Cleaning [P = .027]) also showed an effect of gender with worse scores in women. The nine ADL domains showing effect of time, showed temporary improvement at 12 months follow‐up, most probably due to dopaminergic medication. All nine domains deteriorated at later follow‐up.Conclusions: As expected, there was deterioration in self‐assessed performance in the majority od ADL domains over time. Women assessed their ADLs worse in two domains (Shopping and Cleaning) probably reflecting a general gender‐related activity pattern rather than being a PD‐specific finding.
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