| 1. |
- Memedi, Mevludin, 1983-, et al.
(författare)
-
Computerized identification of motor complications in Parkinson's disease
- 2014
-
Ingår i: Movement Disorders Supplement. - : Wiley-Blackwell. - 0885-3185. ; , s. S187-S188
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Objective: To investigate whether spirography-based objective measures of motor dysfunctions are able to discriminate between Parkinson’s disease (PD) patients with different motor states (Off and Dyskinesia) and healthy elderly (HE) subjects.Background: Sixty-five advanced PD patients and 10 HE subjects performed repeated assessments of spirography, using a touch screen telemetry device. On each test occasion, they were asked to trace a pre-drawn Archimedes spiral using dominant hand and repeating the test three times. The clinical assessment was only performed in the patient group by animating the three spirals in a web interface, allowing a clinician (DN) to observe accelerations and spa-tial changes during the drawing process. A scale ranging from 0 (normal) to 4 (extremely severe) was used for the assessment of kinematic properties of speed, irregularity and hesitation. Finally, the momentary motor state of the patient was marked using two classes: - 1 (Off) and 1 (Dyskinesia). The HE samples were assigned a 0 (On) class and used in subsequent analysis.Methods: After time series analysis, 13 quantitative measures were calculated for representing the severity of symptoms in each individual kinematic property. Principal Component Analysis was then used to reduce their dimensions by retaining the first 4 principal components (PC). To investigate differences in mean PC scores across the three classes a one-way ANOVA test followed by Tukey multiple comparisons was used. An ordinal logistic regression model, using 10-fold cross-validation, was used to map the 4 PC to the corresponding motor state classes.Results: The agreements between computer and clinician ratings were very good with a weighted area under the receiver operating characteristic curve (AUC) coefficient of 0.91 (Table 1). The mean PC scores were different across the three classes, only at different levels (Fig 1). The Spearman’s rank correlations between the first two PC and visually assessed kinematic properties were: speed (PC1, 0.34; PC2, 0.83), irregularity (PC1, 0.17; PC2, 0.17) and hesitation (PC1, 0.27; PC2, 0.77).Conclusions: These findings suggest that spirography-based objective measures are valid measures of spatial- and time-dependent deficits in PD. The differences among the three classes imply that these measures can be used to assess changes in the motor states in response to therapeutic interventions.
|
|
| 2. |
|
|
| 3. |
- Memedi, Mevludin, 1983-, et al.
(författare)
-
Visualization of spirography-based objective measures in Parkinson's disease
- 2014
-
Ingår i: Movement Disorders Supplement. - : Wiley-Blackwell. - 0885-3185. ; , s. S187-S189
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Objective: To investigate whether advanced visualizations of spirography-based objective measures are useful in differentiating motor complications among Parkinson’s disease (PD) patients.Background: Sixty-five patients diagnosed with advanced PD have utilized a telemetry test battery, implemented on a touch screen handheld computer, in a telemedicine setting. On each test occasion, they were asked to perform repeated and time-stamped assessments of spiral drawing performance by tracing a pre-drawn Archimedes spiral. The test battery was also used by 10 healthy elderly (HE) subjects.Methods: A web-based framework was developed to visualize the performance during spirography of both patients and HE subjects to a clinician (DN). The performance was depicted by animating the spiral drawings (Fig 1). In addition, the framework displayed two time series views for representing drawing speed (blue line) and displacement from the ideal trajectory (orange line). The views are coordinated and linked i.e. user interactions in one of the views will be reflected in other views. For instance, when the user points in one of the pixels in spiral view, the circle size of the underlying pixel increases and a vertical line appears in the time series views to depict the corresponding position. Fig 1 shows single randomly selected spirals per each subject group: A) a PD patient in Dyskinesia state, B) a HE subject, and C) a PD patient in Off state.Results: The clinician recognized Dyskinesia symptoms as movements made with high speed, smooth/gradual spatial displacements, and a small amount of hesitation (Fig 1A). Similarly, Off symptoms were associated with low speed, sharp/abrupt spatial displacements, and a large amount of hesitation (Fig 1C). In contrast, the spiral drawn by a HE subject (Fig 1B) was associated with unchanging levels of kinematic features i.e. drawing speed, spatial displacements and hesitation over time.Conclusions: Visualizing spirography-based objective measures enables identification of trends and patterns of motor dysfunctions at the patient’s individual level. Dynamic access of visualized motor tests may be useful during the evaluation of therapy-related complications such as under- and over-medications. This will assist during individualized optimization of therapies, enabling patients to spend more time in the On state with a minimum of Off and dyskinetic states.
|
|
| 4. |
|
|
| 5. |
- Aarsland, D, et al.
(författare)
-
Neuropsychiatric symptoms in Parkinson's disease
- 2009
-
Ingår i: Movement disorders : official journal of the Movement Disorder Society. - : Wiley. - 1531-8257. ; 24:15, s. 2175-2186
-
Tidskriftsartikel (refereegranskat)
|
|
| 6. |
|
|
| 7. |
- Aarsland, D, et al.
(författare)
-
Psychiatric issues in cognitive impairment
- 2014
-
Ingår i: Movement disorders : official journal of the Movement Disorder Society. - : Wiley. - 1531-8257. ; 29:5, s. 651-662
-
Tidskriftsartikel (refereegranskat)
|
|
| 8. |
|
|
| 9. |
- Abdelnour, C., et al.
(författare)
-
Alzheimer's disease cerebrospinal fluid biomarkers predict cognitive decline in lewy body dementia
- 2016
-
Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 31:8, s. 1203-1208
-
Tidskriftsartikel (refereegranskat)abstract
- IntroductionAlzheimer's disease pathologies are common in dementia with Lewy bodies, but their clinical relevance is not clear. CSF biomarkers amyloid beta 1-42, total tau, and tau phosphorylated at threonine 181 reflect Alzheimer's disease neuropathology antemortem. In PD, low CSF amyloid beta 1-42 predict long-term cognitive decline, but little is known about these biomarkers as predictors for cognitive decline in Lewy body dementia. The aim of this study was to assess whether Alzheimer's disease CSF biomarkers predict cognitive decline in Lewy body dementia. MethodsFrom a large European dementia with Lewy bodies multicenter study, we analyzed baseline Alzheimer's disease CSF biomarkers and serial MMSE (baseline and 1- and 2-year follow-up) in 100 patients with Lewy body dementia. Linear mixed-effects analyses, adjusted for sex, age, baseline MMSE, and education, were performed to model the association between CSF biomarkers and rate of cognitive decline measured with MMSE. An Alzheimer's disease CSF profile was defined as pathological amyloid beta 1-42 plus pathological total tau or phosphorylated tau. ResultsThe Alzheimer's disease CSF profile, and pathological levels of amyloid beta 1-42, were associated with a more rapid decline in MMSE (2.2 [P < 0.05] and 2.9 points difference [P < 0.01], respectively). Higher total tau values showed a trend toward association without statistical significance (2.0 points difference; P = 0.064), whereas phosphorylated tau was not associated with decline. ConclusionsReduced levels of CSF amyloid beta 1-42 were associated with more rapid cognitive decline in Lewy body dementia patients. Future prospective studies should include larger samples, centralized CSF analyses, longer follow-up, and biomarker-pathology correlation. (c) 2016 International Parkinson and Movement Disorder Society
|
|
| 10. |
- Abdelnour, C, et al.
(författare)
-
Erratum
- 2019
-
Ingår i: Movement disorders : official journal of the Movement Disorder Society. - : Wiley. - 1531-8257. ; 34:4, s. 593-593
-
Tidskriftsartikel (refereegranskat)
|
|
| 11. |
- Akram, Harith, et al.
(författare)
-
L-Dopa Responsiveness Is Associated With Distinctive Connectivity Patterns in Advanced Parkinson's Disease
- 2017
-
Ingår i: Movement Disorders. - : Wiley-Blackwell. - 0885-3185 .- 1531-8257. ; 32:6, s. 874-883
-
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.
|
|
| 12. |
|
|
| 13. |
- Alonso, Fabiola, et al.
(författare)
-
Comparison of deep brain stimulation systems
- 2014
-
Ingår i: Poster Presentations. - : Wiley. ; , s. 1173-1173
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Objective: To quantitatively compare the electric field generated by voltage and current controlled deep brain stimulation systems.Background: Traditionally deep brain stimulation (DBS) systems have used voltage control however more recently, current controlled systems have been approved to treat Parkinson's disease and related movement disorders. In the endeavor of understanding the behavior of DBS systems a common approach is the use of computer models suitable to simulate the electric field, current density and other related electric parameters.Methods: 2D finite element models based on commercially available DBS systems have been built for each system: I. Model 3389, Medtronic Inc., USA for voltage control; and II. Model 6142, St Jude Medical Inc. USA for current control. The brain tissue has been simplified to homogeneous and isotropic medium. The electric settings correspond to a monopolar configuration, using one of the four contacts available as the active electrode and the outer boundary of the tissue as the reference. Three simulations were performed to mimic different stages of the leads implantation: a) an original stage where the brain tissue is considered as pure gray matter, b) an acute stage that simulates the leakage of cerebral spinal fluid immediately after the electrodes' insertion; and c) a chronic stage mimicking fibrous tissue created around the electrodes some weeks after implantation. Both systems were submitted to the same conditions using as active electrode the third contact from the tip of the lead. The comparison is based on the maximal distance reached by the isopotential of 0.2 V/mm.Results: The simulations showed that voltage controlled stimulation systems are more susceptible to changes in the electrical conductivity of the medium i.e. change over time of the tissue around the electrode. This agrees with the adjustment of the stimulation amplitude often necessary a few weeks postoperatively. Current controlled stimulation in turn, presented a linear behavior of the distance reached at different stimulation amplitudes at all stages.Conclusions: Current controlled stimulation might be a good option due to its linear behavior over time, nevertheless more studies including a more realistic brain model, different designs of DBS electrodes and different electric parameter, are needed to encourage the use of this type of systems.
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
- Ayton, Scott, et al.
(författare)
-
The Neuroinflammatory Acute Phase Response in Parkinsonian-Related Disorders
- 2022
-
Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 37:5, s. 993-1003
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Neuroinflammation is implicated in the pathophysiology of Parkinson's disease (PD) and related conditions, yet prior clinical biomarker data report mixed findings. Objectives: The aim was to measure a panel of neuroinflammatory acute phase response (APR) proteins in the cerebrospinal fluid (CSF) of participants with PD and related disorders. Methods: Eleven APR proteins were measured in the CSF of 867 participants from the BioFINDER cohort who were healthy (612) or had a diagnosis of PD (155), multiple system atrophy (MSA) (26), progressive supranuclear palsy (PSP) (22), dementia with Lewy bodies (DLB) (23), or Parkinson’s disease with dementia (PDD) (29). Results: CSF APR proteins were mostly unchanged in PD, with only haptoglobin and α1-antitrypsin significantly elevated compared to controls. These proteins were variably increased in the other disorders. Certain protein components yielded unique signatures according to diagnosis: ferritin and transthyretin were selectively elevated in MSA and discriminated these patients from all others. Haptoglobin was selectively increased in PSP, discriminating this disease from MSA when used in combination with ferritin and transthyretin. This panel of proteins did not correlate well with severity of motor impairment in any disease category, but several (particularly ceruloplasmin and ferritin) were associated with memory performance (Mini-Mental State Examination) in patients with DLB and PDD. Conclusions: These findings provide new insights into inflammatory changes in PD and related disorders while also introducing biomarkers of potential clinical diagnostic utility.
|
|
| 18. |
|
|
| 19. |
- Barbu, Andrea R, et al.
(författare)
-
Gene Therapy
- 2010. - 4th edition
-
Ingår i: Textbook of Diabetes. - Thousand Oaks, CA : Wiley-Blackwell. - 9781405191814 ; 25, s. 604-604
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
- Bezard, Erwan, et al.
(författare)
-
Animal Models of Parkinson's Disease: Limits and Relevance to Neuroprotection Studies
- 2013
-
Ingår i: Movement Disorders. - : Wiley. - 0885-3185. ; 28:1, s. 61-70
-
Forskningsöversikt (refereegranskat)abstract
- Over the last two decades, significant strides has been made toward acquiring a better knowledge of both the etiology and pathogenesis of Parkinson's disease (PD). Experimental models are of paramount importance to obtain greater insights into the pathogenesis of the disease. Thus far, neurotoxin-based animal models have been the most popular tools employed to produce selective neuronal death in both in vitro and in vivo systems. These models have been commonly referred to as the pathogenic models. The current trend in modeling PD revolves around what can be called the disease gene-based models or etiologic models. The value of utilizing multiple models with a different mechanism of insult rests on the premise that dopamine-producing neurons die by stereotyped cascades that can be activated by a range of insults, from neurotoxins to downregulation and overexpression of disease-related genes. In this position article, we present the relevance of both pathogenic and etiologic models as well as the concept of clinically relevant designs that, we argue, should be utilized in the preclinical development phase of new neuroprotective therapies before embarking into clinical trials. (C) 2012 Movement Disorder Society
|
|
| 25. |
- Bezard, Erwan, et al.
(författare)
-
Study of the antidyskinetic effect of eltoprazine in animal models of levodopa-induced dyskinesia
- 2013
-
Ingår i: Movement Disorders. - : Wiley. - 0885-3185. ; 28:8, s. 1088-1096
-
Tidskriftsartikel (refereegranskat)abstract
- The serotonin (5-hydroxytryptamine [5HT]) system has recently emerged as an important player in the appearance of l-3,4-dihydroxyphenylalanine (levodopa [l-dopa])-induced dyskinesia in animal models of Parkinson's disease. In fact, dopamine released as a false transmitter from serotonin neurons appears to contribute to the pulsatile stimulation of dopamine receptors, leading to the appearance of the abnormal involuntary movements. Thus, drugs able to dampen the activity of serotonin neurons hold promise for the treatment of dyskinesia. The authors investigated the ability of the mixed 5-HT 1A/1B receptor agonist eltoprazine to counteract l-dopa-induced dyskinesia in 6-hydroxydopamine-lesioned rats and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaques. The data demonstrated that eltoprazine is extremely effective in suppressing dyskinesia in experimental models, although this effect was accompanied by a partial worsening of the therapeutic effect of l-dopa. Interestingly, eltoprazine was found to (synergistically) potentiate the antidyskinetic effect of amantadine. The current data indicated that eltoprazine is highly effective in counteracting dyskinesia in preclinical models. However, the partial worsening of the l-dopa effect observed after eltoprazine administration represents a concern; whether this side effect is due to a limitation of the animal models or to an intrinsic property of eltoprazine needs to be addressed in ongoing clinical trials. The data also suggest that the combination of low doses of eltoprazine with amantadine may represent a valid strategy to increase the antidyskinetic effect and reduce the eltoprazine-induced worsening of l-dopa therapeutic effects. (c) 2013 Movement Disorder Society
|
|
