| 1. |
- Donadio, Vincenzo, et al.
(författare)
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Phosphorylated α-synuclein in skin Schwann cells : a new biomarker for multiple system atrophy
- 2023
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Ingår i: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 146:3, s. 1065-1074
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Tidskriftsartikel (refereegranskat)abstract
- Multiple system atrophy (MSA) is characterized by accumulation of phosphorylated α-synuclein (p-syn) as glial cytoplasmic inclusions in the brain and a specific biomarker for this disorder is urgently needed. We aimed at investigating if p-syn can also be detected in skin Remak non-myelinating Schwann cells (RSCs) as Schwann cell cytoplasmic inclusions (SCCi) and may represent a reliable clinical biomarker for MSA.This cross-sectional diagnostic study evaluated skin p-syn in 96 patients: 46 with probable MSA (29 with parkinsonism type MSA and 17 with cerebellar type MSA), 34 with Parkinson's disease (PD) and 16 with dementia with Lewy bodies (DLB). We also included 50 healthy control subjects. Patients were recruited from five different medical centres. P-syn aggregates in skin sections were stained by immunofluorescence, followed by analyses with confocal microscopy and immuno-electron microscopy. All analyses were performed in a blinded fashion.Overall, p-syn aggregates were found in 78% of MSA patients and 100% of patients with PD/DLB, whereas they could not be detected in controls. As for neuronal aggregates 78% of MSA patients were positive for p-syn in somatic neurons, whereas all PD/DLB patients were positive in autonomic neurons. When analysing the presence of p-syn in RSCs, 74% of MSA patients were positive, whereas no such SCCi could be observed in PD/DLB patients. Analyses by immuno-electron microscopy confirmed that SCCi were only found in cases with MSA and thus absent in those with PD/DLB.In conclusion, our findings demonstrate that (i) fibrillar p-syn in RSCs is a pathological hallmark of MSA and may be used as a specific and sensitive disease biomarker; (ii) in Lewy body synucleinopathies (PD/DLB) only neurons contain p-syn deposits; and (iii) the cell-specific deposition of p-syn in the skin thus mirrors that of the brain in many aspects and suggests that non-myelinated glial cells are also involved in the MSA pathogenesis.
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| 2. |
- Kristiansen, Ivar, et al.
(författare)
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Short-Term Cost and Health Consequences of Duodenal Levodopa Infusion in Advanced Parkinson's Disease in Sweden : An Exploratory Study
- 2009
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Ingår i: Applied Health Economics and Health Policy. - 1175-5652 .- 1179-1896. ; 7:3, s. 167-180
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Tidskriftsartikel (refereegranskat)abstract
- Levodopa is the cornerstone treatment for Parkinson's disease, but the short half-life of levodopa limits its usefulness in late stages of the disease. Duodenal levodopa infusion (DLI) allows more stable plasma levels and better motor symptom control. To explore the costs and health benefits of replacing conventional oral polypharmacy with DLI in patients with advanced Parkinson's disease, from a Swedish healthcare payer perspective. Based on a clinical, randomized, crossover study with 24 patients (DIREQT), a decision analytic model predicted 2-year drug costs and QALYs for conventional oral therapy and for DLI. Health-related quality of life (HR-QOL) was recorded using a 15-dimensional (15D) utility instrument at baseline and during the two 3-week trial periods, and then at eight follow-up visits during the subsequent 6 months. Use of medication was based on data from DIREQT and previous studies. Unit costs were based on market prices (drugs) and customary charges in Sweden. All costs were expressed in Swedish kronor (SEK), year 2004 values (&U20AC;1.00 approximately SEK9.17, $US1.00 = SEK7.47). Future costs and outcomes were discounted at 3%. One-way and probabilistic sensitivity analyses were conducted. The mean utility scores were 0.77 for DLI and 0.72 for conventional therapy (p = 0.02). A considerable variation in the scores was observed during the study. The expected per-patient 2-year cost of DLI was SEK562 000 while it was SEK172 000 for conventional therapy. The mean number of QALYs was 1.48 and 1.42, respectively, representing an incremental cost of SEK6.1 million per QALY for DLI (all values discounted at 3%). Using other assumptions in sensitivity analyses, the cost per QALY could be as low as SEK456 000. This analysis can be considered exploratory only; it is based on very limited data. Nevertheless, our findings suggest that DLI results in a significant improvement in HR-QOL. However, the cost per QALY is likely to be higher than customary cost-effectiveness thresholds. Whether these benefits justify the additional costs depends on how the health benefits are measured and how these benefits are valued by society.
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| 3. |
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| 4. |
- Aghanavesi, Somayeh, 1981-, et al.
(författare)
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A multiple motion sensors index for motor state quantification in Parkinson's disease
- 2020
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Ingår i: Computer Methods and Programs in Biomedicine. - : Elsevier BV. - 0169-2607 .- 1872-7565. ; 189
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To construct a Treatment Response Index from Multiple Sensors (TRIMS) for quantification of motor state in patients with Parkinson's disease (PD) during a single levodopa dose. Another aim was to compare TRIMS to sensor indexes derived from individual motor tasks. Method: Nineteen PD patients performed three motor tests including leg agility, pronation-supination movement of hands, and walking in a clinic while wearing inertial measurement unit sensors on their wrists and ankles. They performed the tests repeatedly before and after taking 150% of their individual oral levodopa-carbidopa equivalent morning dose.Three neurologists blinded to treatment status, viewed patients’ videos and rated their motor symptoms, dyskinesia, overall motor state based on selected items of Unified PD Rating Scale (UPDRS) part III, Dyskinesia scale, and Treatment Response Scale (TRS). To build TRIMS, out of initially 178 extracted features from upper- and lower-limbs data, 39 features were selected by stepwise regression method and were used as input to support vector machines to be mapped to mean reference TRS scores using 10-fold cross-validation method. Test-retest reliability, responsiveness to medication, and correlation to TRS as well as other UPDRS items were evaluated for TRIMS. Results: The correlation of TRIMS with TRS was 0.93. TRIMS had good test-retest reliability (ICC = 0.83). Responsiveness of the TRIMS to medication was good compared to TRS indicating its power in capturing the treatment effects. TRIMS was highly correlated to dyskinesia (R = 0.85), bradykinesia (R = 0.84) and gait (R = 0.79) UPDRS items. Correlation of sensor index from the upper-limb to TRS was 0.89. Conclusion: Using the fusion of upper- and lower-limbs sensor data to construct TRIMS provided accurate PD motor states estimation and responsive to treatment. In addition, quantification of upper-limb sensor data during walking test provided strong results. © 2019
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| 5. |
- Aghanavesi, Somayeh, 1981-, et al.
(författare)
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Feasibility of a multi-sensor data fusion method for assessment of Parkinson’s disease motor symptoms
- 2018
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Title: Feasibility of a multi-sensor data fusion method for assessment of Parkinson’s disease motor symptomsObjective: To assess the feasibility of measuring Parkinson’s disease (PD) motor symptoms with a multi-sensor data fusion method. More specifically, the aim is to assess validity, reliability and sensitivity to treatment of the methods.Background: Data from 19 advanced PD patients (Gender: 14 males and 5 females, mean age: 71.4, mean years with PD: 9.7, mean years with levodopa: 9.5) were collected in a single center, open label, single dose clinical trial in Sweden [1].Methods: The patients performed leg agility and 2-5 meter straight walking tests while wearing motion sensors on their limbs. They performed the tests at baseline, at the time they received the morning dose, and at pre-specified time points until the medication wore off. While performing the tests the patients were video recorded. The videos were observed by three movement disorder specialists who rated the symptoms using a treatment response scale (TRS), ranging from -3 (very off) to 3 (very dyskinetic). The sensor data consisted of lower limb data during leg agility, upper limb data during walking, and lower limb data during walking. Time series analysis was performed on the raw sensor data extracted from 17 patients to derive a set of quantitative measures, which were then used during machine learning to be mapped to mean ratings of the three raters on the TRS scale. Combinations of data were tested during the machine learning procedure.Results: Using data from both tests, the Support Vector Machines (SVM) could predict the motor states of the patients on the TRS scale with a good agreement in relation to the mean ratings of the three raters (correlation coefficient = 0.92, root mean square error = 0.42, p<0.001). Additionally, there was good test-retest reliability of the SVM scores during baseline and second tests with intraclass-correlation coefficient of 0.84. Sensitivity to treatment for SVM was good (Figure 1), indicating its ability to detect changes in motor symptoms. The upper limb data during walking was more informative than lower limb data during walking since SVMs had higher correlation coefficient to mean ratings. Conclusions: The methodology demonstrates good validity, reliability, and sensitivity to treatment. This indicates that it could be useful for individualized optimization of treatments among PD patients, leading to an improvement in health-related quality of life.
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| 6. |
- Aghanavesi, Somayeh, 1981-, et al.
(författare)
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Motion sensor-based assessment of Parkinson's disease motor symptoms during leg agility tests : results from levodopa challenge
- 2020
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Ingår i: IEEE journal of biomedical and health informatics. - : IEEE Computer Society. - 2168-2194 .- 2168-2208. ; 24:1, s. 111-118
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson's disease (PD) is a degenerative, progressive disorder of the central nervous system that mainly affects motor control. The aim of this study was to develop data-driven methods and test their clinimetric properties to detect and quantify PD motor states using motion sensor data from leg agility tests. Nineteen PD patients were recruited in a levodopa single dose challenge study. PD patients performed leg agility tasks while wearing motion sensors on their lower extremities. Clinical evaluation of video recordings was performed by three movement disorder specialists who used four items from the motor section of the Unified PD Rating Scale (UPDRS), the treatment response scale (TRS) and a dyskinesia score. Using the sensor data, spatiotemporal features were calculated and relevant features were selected by feature selection. Machine learning methods like support vector machines (SVM), decision trees and linear regression, using 10-fold cross validation were trained to predict motor states of the patients. SVM showed the best convergence validity with correlation coefficients of 0.81 to TRS, 0.83 to UPDRS #31 (body bradykinesia and hypokinesia), 0.78 to SUMUPDRS (the sum of the UPDRS items: #26-leg agility, #27-arising from chair and #29-gait), and 0.67 to dyskinesia. Additionally, the SVM-based scores had similar test-retest reliability in relation to clinical ratings. The SVM-based scores were less responsive to treatment effects than the clinical scores, particularly with regards to dyskinesia. In conclusion, the results from this study indicate that using motion sensors during leg agility tests may lead to valid and reliable objective measures of PD motor symptoms.
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| 7. |
- Aghanavesi, Somayeh, 1981-, et al.
(författare)
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Objective assessment of Parkinson’s disease motor symptoms during leg agility test using motion sensors
- 2018
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Konferensbidrag (refereegranskat)abstract
- Title: Objective assessment of Parkinson’s disease motor symptoms during leg agility test using motion sensorsObjective: To develop and evaluate machine learning methods for assessment of Parkinson’s disease (PD) motor symptoms using leg agility (LA) data collected with motion sensors during a single dose experiment.Background: Nineteen advanced PD patients (Gender: 14 males and 5 females, mean age: 71.4, mean years with PD: 9.7, mean years with levodopa: 9.5) were recruited in a single center, open label, single dose clinical trial in Sweden [1].Methods: The patients performed up to 15 LA tasks while wearing motions sensors on their foot ankle. They performed tests at pre-defined time points starting from baseline, at the time they received a morning dose (150% of their levodopa equivalent morning dose), and at follow-up time points until the medication wore off. The patients were video recorded while performing the motor tasks. and three movement disorder experts rated the observed motor symptoms using 4 items from the Unified PD Rating Scale (UPDRS) motor section including UPDRS #26 (leg agility), UPDRS #27 (Arising from chair), UPDRS #29 (Gait), UPDRS #31 (Body Bradykinesia and Hypokinesia), and dyskinesia scale. In addition, they rated the overall mobility of the patients using Treatment Response Scale (TRS), ranging from -3 (very off) to 3 (very dyskinetic). Sensors data were processed and their quantitative measures were used to develop machine learning methods, which mapped them to the mean ratings of the three raters. The quality of measurements of the machine learning methods was assessed by convergence validity, test-retest reliability and sensitivity to treatment.Results: Results from the 10-fold cross validation showed good convergent validity of the machine learning methods (Support Vector Machines, SVM) with correlation coefficients of 0.81 for TRS, 0.78 for UPDRS #26, 0.69 for UPDRS #27, 0.78 for UPDRS #29, 0.83 for UPDRS #31, and 0.67 for dyskinesia scale (P<0.001). There were good correlations between scores produced by the methods during the first (baseline) and second tests with coefficients ranging from 0.58 to 0.96, indicating good test-retest reliability. The machine learning methods had lower sensitivity than mean clinical ratings (Figure. 1).Conclusions: The presented methodology was able to assess motor symptoms in PD well, comparable to movement disorder experts. The leg agility test did not reflect treatment related changes.
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| 8. |
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| 9. |
- Aghanavesi, Somayeh, 1981-, et al.
(författare)
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Treatment response index from a multi-modal sensor fusion platform for assessment of motor states in Parkinson's disease
- 2019
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this paper is to develop and evaluate a multi-sensor data fusion platform for quantifying Parkinson’s disease (PD) motor states. More specifically, the aim is to evaluate the clinimetric properties (validity, reliability, and responsiveness to treatment) of the method, using data from motion sensors during lower- and upper-limb tests.Methods: Nineteen PD patients and 22 healthy controls were recruited in a single center study. Subjects performed standardized motor tasks of Unified PD Rating Scale (UPDRS), including leg agility, hand rotation, and walking after wearing motion sensors on ankles and wrists. PD patients received a single levodopa dose before and at follow-up time points after the dose administration. Patients were video recorded and their motor symptoms were rated by three movement disorder experts. Experts rated each and every test occasions based on the six items of UPDRS-III (motor section), the treatment response scale (TRS) and the dyskinesia score. Spatiotemporal features were extracted from the sensor data. Features from lower limbs and upper limbs were fused. Feature selection methods of stepwise regression (SR), Lasso regression and principle component analysis (PCA) were used to select the most important features. Different machine learning methods of linear regression (LR), decision trees, and support vector machines were examined and their clinimetric properties were assessed.Results: Treatment response index from multimodal motion sensors (TRIMMS) scores obtained from the most valid method of LR when using data from all tests. Features were selected by SR, and this method resulted in r=0.95 to TRS. The test-retest reliability of TRIMMS was good with intra-class correlation coefficient of 0.82. Responsiveness of the TRIMMS to levodopa treatment was similar to the responsiveness of TRS.Conclusions: The results from this study indicate that fusing motion sensors data gathered during standardized motor tasks leads to valid, reliable and sensitive objective measurements of PD motor symptoms. These measurements could be further utilized in studies for individualized optimization of treatments in PD.
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| 10. |
- Aghanavesi, Somayeh, 1981-, et al.
(författare)
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Verification of a Method for Measuring Parkinson's Disease Related Temporal Irregularity in Spiral Drawings
- 2017
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Ingår i: Sensors. - Basel : MDPI AG. - 1424-8220. ; 17:10
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Tidskriftsartikel (refereegranskat)abstract
- -value = 0.02). Test-retest reliability of TIS was good with Intra-class Correlation Coefficient of 0.81. When assessing changes in relation to treatment, TIS contained some information to capture changes from Off to On and wearing off effects. However, the correlations between TIS and clinical scores (UPDRS and Dyskinesia) were weak. TIS was able to differentiate spiral drawings drawn by patients in an advanced stage from those drawn by healthy subjects, and TIS had good test-retest reliability. TIS was somewhat responsive to single-dose levodopa treatment. Since TIS is an upper limb high-frequency-based measure, it cannot be detected during clinical assessment.
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| 11. |
- Ahmed, Mobyen Uddin, et al.
(författare)
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A fuzzy rule-based decision support system for Duodopa treatment in Parkinson
- 2006
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Ingår i: 23rd annual workshop of the Swedish Artificial Intelligence Society. - Umeå.
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Konferensbidrag (refereegranskat)abstract
- A decision support system (DSS) was implemented based on a fuzzy logic inference system (FIS) to provide assistance in dose alteration of Duodopa infusion in patients with advanced Parkinson’s disease, using data from motor state assessments and dosage. Three-tier architecture with an object oriented approach was used. The DSS has a web enabled graphical user interface that presents alerts indicating non optimal dosage and states, new recommendations, namely typical advice with typical dose and statistical measurements. One data set was used for design and tuning of the FIS and another data set was used for evaluating performance compared with actual given dose. Overall goodness-of-fit for the new patients (design data) was 0.65 and for the ongoing patients (evaluation data) 0.98. User evaluation is now ongoing. The system could work as an assistant to clinical staff for Duodopa treatment in advanced Parkinson’s disease.
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| 12. |
- Appel, Lieuwe, et al.
(författare)
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Use of C-11-PE2I PET in Differential Diagnosis of Parkinsonian Disorders
- 2015
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 56:2, s. 234-242
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Tidskriftsartikel (refereegranskat)abstract
- In idiopathic Parkinson disease and atypical parkinsonian disorders, central dopaminergic and overall brain functional activity are altered to different degrees, causing difficulties in achieving an unambiguous clinical diagnosis. A dual examination using I-123-FP-CIT (I-123-N-omega-fluoropropyl- 2 beta-carbomethoxy-3 beta-(4-iodophenyl) nortropane, or I-123-ioflupane) SPECT and F-18-FDG PET provides complementary information on dopamine transporter (DAT) availability and overall brain functional activity, respectively. Parametric images based on a single, dynamic C-11-PE2I (N-(3-iodoprop-2E-enyl)-2 beta-carbomethoxy-3 beta-(4-methyl-phenyl) nortropane) scan potentially supply both DAT availability (nondisplaceable binding potential [BPND]) and relative cerebral blood flow (relative delivery [R-1]) at voxel level. This study aimed to evaluate the validity of C-11-PE2I PET against the dual-modality approach using I-123-FP-CIT SPECT and F-18-FDG PET.Methods: Sixteen patients with parkinsonian disorders had a dual examination with F-18-FDG PET and I-123-FP-CIT SPECT following clinical routines and additionally an experimental C-11-PE2I PET scan. Parametric BPND and R-1 images were generated using receptor parametric mapping with the cerebellum as a reference. T1-weighted MR imaging was used for automated definition of volumes of interest (VOI). The DAT VOIs included the basal ganglia, whereas the overall brain functional activity was examined using VOIs across the brain. BPND and R-1 values were compared with normalized I-123-FP-CIT and F-18-FDG uptake values, respectively, using Pearson correlations and regression analyses. In addition, 2 masked interpreters evaluated the images visually, in both the routine and the experimental datasets, for comparison of patient diagnoses.Results: Parametric C-11-PE2I BPND and R-1 images showed high consistency with I-123-FP-CIT SPECT and F-18-FDG PET images. Correlations between C-11-PE2I BPND and I-123-FP-CIT uptake ratios were 0.97 and 0.76 in the putamen and caudate nucleus, respectively. Regional C-11-PE2I R-1 values were moderately to highly correlated with normalized F-18-FDG values (range, 0.61-0.94). Visual assessment of DAT availability showed a high consistency between C-11-PE2I BPND and I-123-FP-CIT images, whereas the consistency was somewhat lower for appraisal of overall brain functional activity using I-123-FP-CIT and F-18-FDG images. Substantial differences were found between clinical diagnosis and both neuro-imaging diagnoses.Conclusion: A single, dynamic C-11-PE2I PET investigation is a powerful alternative to a dual examination with I-123-FP-CIT SPECT and F-18-FDG PET for differential diagnosis of parkinsonian disorders. A large-scale patient study is, however, needed to further investigate distinct pathologic patterns in overall brain functional activity for various parkinsonian disorders.
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| 13. |
- Aquilonius, Sten-Magnus, et al.
(författare)
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Development of new levodopa treatment strategies in Parkinson’s disease – from bedside to bench to bedside
- 2017
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Ingår i: Upsala Journal of Medical Sciences. - 0300-9734 .- 2000-1967. ; 122:2, s. 71-77
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Forskningsöversikt (refereegranskat)abstract
- This review will illustrate the process of moving from an idea through preclinical research and Galenic developments into clinical investigations and finally to approval by regulatory agencies within the European Union. The two new treatment strategies described, levodopa/carbidopa intestinal gel and levodopa/carbidopa microtablets, for advanced Parkinson's disease, have been developed in collaborative research within departments at Uppsala University. With this historical approach, reference priority is given to reports considered to be of special importance for this more than two decades long process from bedside to bench to bedside'.
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| 14. |
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| 15. |
- Bergquist, Filip, 1970, et al.
(författare)
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Motor Efficacy of Subcutaneous DIZ102, Intravenous DIZ101 or Intestinal Levodopa/Carbidopa Infusion
- 2024
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Ingår i: MOVEMENT DISORDERS CLINICAL PRACTICE. - 2330-1619.
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Tidskriftsartikel (refereegranskat)abstract
- Background: It has been suggested that carbidopa at high blood concentrations may counter the therapeutic effect of levodopa in Parkinson's disease by entering the brain and blocking central levodopa conversion to dopamine. We previously demonstrated equivalent plasma levodopa concentration in patients with Parkinson's disease during 16 h of (1) intravenous carbidopa/levodopa (DIZ101) infusion, (2) subcutaneous carbidopa/levodopa (DIZ102) infusion or (3) intestinal carbidopa/levodopa gel infusion. Plasma levels of carbidopa were however approximately four times higher with DIZ101 and DIZ102 than with LCIG, and higher than those usually observed with oral levodopa/carbidopa. Objectives: To investigate if high carbidopa blood concentrations obtained with parenteral levodopa/carbidopa (ratio 8:1) counter the effect of levodopa on motor symptoms. Methods: Eighteen patients with advanced Parkinson's disease were administered DIZ101, DIZ102, and intestinal levodopa/carbidopa gel for 16 h on different days in randomized order. Video recordings of a subset of the motor examination in the Unified Parkinson's Disease Rating Scale (UPDRS) were evaluated by raters blinded for treatment and time. Motor function was also measured using a wrist-worn device monitoring bradykinesia, dyskinesia, and tremor (Parkinson KinetiGraph). Results: There was no tendency for poorer levodopa effect with DIZ101 or DIZ102 as compared to LCIG. Conclusion: Although DIZ101 or DIZ102 causes approximately four times higher plasma carbidopa levels than LCIG, patients responded equally well to all treatments. The results do not indicate that high plasma carbidopa levels hamper the motor efficacy of levodopa.
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| 16. |
- Bergquist, Filip, et al.
(författare)
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Parkinsons sjukdom – heterogen och komplex i sitt kliniska uttryck - Individuella kombinationer av symtom som ändrar sig över tid kräver behandlingsjusteringar och anpassningar
- 2020
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Ingår i: Läkartidningen. - 0023-7205. ; 117
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson's disease is the second most common neurodegenerative disease. Lewy bodies with alpha-synuclein as the major component and loss of dopaminergic nerve cells in substantia nigra are neuropathological features. The diagnosis of Parkinson's disease is based on the occurrence of bradykinesia, rigidity and resting tremor. The disease is also associated with several non-motor symptoms. The therapy is mainly based on pharmacological treatment to increase dopamine signaling and neurosurgical deep brain stimulation. The symptoms and signs of the progressive disease change over time, requiring treatment adjustments. Patients should be followed by a physician, nurse and a multidisciplinary team with expertise in Parkinson's disease.
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| 17. |
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| 18. |
- Bergquist, Filip, et al.
(författare)
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Parkinsons sjukdom [Parkinsons disease] : heterogen och komplex i sitt kliniska uttryck [heterogeneous and complex in its clinical presentation]
- 2020
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Ingår i: Läkartidningen. - : Sveriges Läkarförbund. - 0023-7205 .- 1652-7518. ; 117
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Tidskriftsartikel (refereegranskat)abstract
- Parkinsons disease is the second most common neurodegenerative disease. Lewy bodies with alpha-synuclein as the major component and loss of dopaminergic nerve cells in substantia nigra are neuropathological features. The diagnosis of Parkinsons disease is based on the occurrence of bradykinesia, rigidity and resting tremor. The disease is also associated with several non-motor symptoms. The therapy is mainly based on pharmacological treatment to increase dopamine signaling and neurosurgical deep brain stimulation. The symptoms and signs of the progressive disease change over time, requiring treatment adjustments. Patients should be followed by a physician, nurse and a multidisciplinary team with expertise in Parkinsons disease.
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| 19. |
- Bergquist, Filip, et al.
(författare)
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Pharmacokinetics of Intravenously (DIZ101), Subcutaneously (DIZ102), and Intestinally (LCIG) Infused Levodopa in Advanced Parkinson Disease
- 2022
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Ingår i: Neurology. - : Lippincott, Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 99:10, s. E965-E976
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives Intestinal levodopa/carbidopa gel infusion (LCIG) is superior to oral treatment in advanced Parkinson disease. The primary objective of this trial was to investigate whether continuous subcutaneous or intravenous infusion with a continuously buffered acidic levodopa/carbidopa solution yields steady-state plasma concentrations of levodopa that are equivalent in magnitude, and noninferior in variability, to those obtained with LCIG in patients with advanced Parkinson disease. Methods A concentrated acidic levodopa/carbidopa (8:1) solution buffered continuously and administered intravenously (DIZ101) or subcutaneously (DIZ102) was compared with an approved LCIG in a randomized, 3-period crossover, open-label, multicenter trial. Formulations were infused for 16 hours to patients with Parkinson disease who were using LCIG as their regular treatment. Patients were recruited from several university neurology clinics but came to the same phase I unit for treatment. Pharmacokinetic variables and safety including dermal tolerance are reported. The primary outcomes were bioequivalence and noninferior variability of DIZ101 and DIZ102 vs LCIG with respect to levodopa plasma concentrations. Results With dosing adjusted to estimated bioavailability, DIZ101 and DIZ102 produced levodopa plasma levels within standard bioequivalence limits compared with LCIG in the 18 participants who received all treatments. Although the levodopa bioavailability for DIZ102 was complete, it was 80% for LCIG. Therapeutic concentrations of levodopa were reached as quickly with subcutaneous administration of DIZ102 as with LCIG and remained stable throughout the infusions. Owing to poor uptake of LCIG, carbidopa levels in plasma were higher with DIZ101 and DIZ102 than with the former. All individuals receiving any of the treatments (n = 20) were included in the evaluation of safety and tolerability. Reactions at the infusion sites were mild and transient. Discussion It is feasible to rapidly achieve high and stable levodopa concentrations by means of continuous buffering of a subcutaneously administered acidic levodopa/carbidopa-containing solution.
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| 20. |
- Bergquist, Filip, et al.
(författare)
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Rörelsestörningar
- 2020
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Ingår i: Neurologi. - : Liber. - 9789147128587
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 21. |
- Braun, Madelen, et al.
(författare)
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Higher levels of neurofilament light chain and total tau in CSF are associated with negative outcome after shunt surgery in patients with normal pressure hydrocephalus
- 2022
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Ingår i: Fluids and Barriers of the CNS. - : Springer Science and Business Media LLC. - 2045-8118. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Lumbar punctures are a common examination in the work-up of patients with idiopathic normal pressure hydrocephalus (iNPH) and cerebrospinal fluid (CSF) biomarkers should therefore be available for use in selection of shunt candidates. The aim of this study was to investigate if CSF biomarkers are associated with outcome after shunt surgery alone or in combination with comorbidity and imaging markers, and investigate associations between CSF biomarkers and symptoms. Methods Preoperative CSF biomarkers were analyzed in 455 patients operated with shunt surgery for iNPH at a single center during 2011-2018. Symptoms before and 12 months after shunt surgery were graded with the Swedish iNPH scale. Neurofilament light chain protein (NfL), total tau (T-tau), phosphorylated tau (P-tau) and amyloid beta1-42 (A beta 1-42) CSF levels were measured. Evans' index and disproportionately enlarged subarachnoid space hydrocephalus were measured on preoperative CT-scans. Preoperative evaluation and follow-up 12 months after shunt surgery were available in 376 patients. Results Higher levels of NfL and T-tau were associated with less improvement after shunt surgery (beta = - 3.10, p = 0.016 and beta = - 2.45, p = 0.012, respectively). Patients whose symptoms deteriorated after shunt surgery had higher preoperative levels of NfL (1250 ng/L [IQR:1020-2220] vs. 1020 [770-1649], p < 0.001) and T-tau (221 ng/L [IQR: 159-346] vs. 190 [135-261], p = 0.0039) than patients with postoperative improvement on the iNPH scale. Among the patients who improved >= 5 levels on the iNPH scale (55%), NfL was abnormal in 22%, T-tau in 14%, P-tau in 6% and A beta 1-42 in 45%, compared with normal reference limits. The inclusion of CSF biomarkers, imaging markers and comorbidity in multivariate predictive Orthogonal Projections to Latent Structures (OPLS) models to did not improve predictability in outcome after shunt surgery. Conclusions Higher levels of T-tau and NfL were associated with a less favorable response to shunt surgery, suggesting a more active neurodegeneration in this group of patients. However, CSF levels of these biomarkers can be elevated also in patients who respond to shunt surgery. Thus, none of these CSF biomarkers, alone or used in combination, are suitable for excluding patients from surgery.
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| 22. |
- Braun, Madelen, et al.
(författare)
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Levels of inflammatory cytokines MCP-1, CCL4, and PD-L1 in CSF differentiate idiopathic normal pressure hydrocephalus from neurodegenerative diseases
- 2023
-
Ingår i: Fluids and Barriers of the CNS. - : BioMed Central (BMC). - 2045-8118. ; 20
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Neuroinflammatory processes have been suggested to play a role in the pathophysiology of neurodegenerative diseases and post-hemorrhagic hydrocephalus, but have rarely been investigated in patients with idiopathic normal pressure hydrocephalus (iNPH). The aim of this study was to investigate whether levels of inflammatory proteins in CSF are different in iNPH compared to healthy controls and patients with selected neurodegenerative disorders, and whether any of these markers can aid in the differential diagnosis of iNPH.Methods: Lumbar CSF was collected from 172 patients from a single center and represented iNPH (n = 74), Alzheimer's disease (AD) (n = 21), mild cognitive impairment (MCI) due to AD (n = 21), stable MCI (n = 22), frontotemporal dementia (n = 13), and healthy controls (HC) (n = 21). Levels of 92 inflammatory proteins were analyzed using a proximity extension assay. As a first step, differences between iNPH and HC were investigated, and proteins that differed between iNPH and HC were then compared with those from the other groups. The linear regressions were adjusted for age, sex, and plate number.Results: Three proteins showed higher (MCP-1, p = 0.0013; CCL4, p = 0.0008; CCL11, p = 0.0022) and one lower (PD-L1, p = 0.0051) levels in patients with iNPH compared to HC. MCP-1 was then found to be higher in iNPH than in all other groups. CCL4 was higher in iNPH than in all other groups, except in MCI due to AD. PD-L1 was lower in iNPH compared to all other groups, except in stable MCI. Levels of CCL11 did not differ between iNPH and the differential diagnoses. In a model based on the four proteins mentioned above, the mean area under the receiver operating characteristic curve used to discriminate between iNPH and the other disorders was 0.91.Conclusions: The inflammatory cytokines MCP-1 and CCL4 are present at higher-and PD-L1 at lower-levels in iNPH than in the other investigated diagnoses. These three selected cytokines may have diagnostic potential in the work-up of patients with iNPH.
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| 23. |
- Bredenberg, Susanne, et al.
(författare)
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An automatic dose dispenser for microtablets : A new concept for individual dosage of drugs in tablet form
- 2003
-
Ingår i: International Journal of Pharmaceutics. - 0378-5173. ; 261:1-2, s. 137-146
-
Tidskriftsartikel (refereegranskat)abstract
- A new concept for individualising the dosage of drugs in solid form is presented. The principle is based on the use of standardised units (microtablets), each containing a subtherapeutic amount of the active ingredient. The required dose is fine-tuned by counting out a specific number of these units. The microtablets are counted electronically from the attached cassette by the automatic dispensing device. The individual dose is set and the dispenser counts and delivers the correct number of microtablets. The usefulness of the automatic dispenser concept and acceptability of the apparatus were evaluated in patients with Parkinson’s disease (PD). After initial instruction on use of the dispenser, 20 patients operated it themselves. All patients were generally satisfied with their management of the automatic dispenser and most would be happy to use the device again. Further technical development is required before use in clinical practice, but the current prototype may be acceptable for some patients. It is concluded that the final version of the automatic dose dispenser concept will offer potential for improvement of drug administration for patients with PD or other diseases requiring individual dosage.
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| 24. |
- Burman, Joachim, 1974-, et al.
(författare)
-
Den neurologiska konsultationen
- 2020
-
Ingår i: Neurologi. - : Liber. - 9789147128587
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Neurologi är en pedagogisk lärobok med förankring i diagnostisk och terapeutisk tradition i Sverige. I denna sjätte upplaga har texten genomgått en omfattande revision. Boken har fått en helt ny disposition samt ett nytt kapitel om funktionella neurologiska sjukdomar. Även i denna upplaga betonas alltjämt neurologins fundament, dvs. noggrann anamnes, somatisk undersökning och klinisk analys.
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| 25. |
- Burman, Joachim, 1974-, et al.
(författare)
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Neurologisk symtomlära
- 2020
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Ingår i: Neurologi. - : Liber. - 9789147128587
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 26. |
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| 27. |
- Busk, Karin, et al.
(författare)
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Long-term efficacy and safety with continuous dopaminergic stimulation pump treatments in Parkinson's disease
- 2011
-
Ingår i: European Neurological Review. - 1758-3837. ; 6:3, s. 156-160
-
Tidskriftsartikel (refereegranskat)abstract
- Continuous dopaminergic stimulation (CDS) is important for symptom control in advanced stages of Parkinson’s disease (PD). The most efficacious approaches are pump treatments with dopaminergic drugs: subcutaneous infusion of the dopamine receptor agonist apomorphine and intestinal infusion of levodopa/carbidopa gel. Both methods decrease motor fluctuations in long-term follow-ups, including parkinsonian and dyskinetic states, when compared to conventional optimised oral therapy. Also non-motor symptoms may be improved. Adverse drug reactions are usually less pronounced although high levodopa doses, which are common with levodopa/carbidopa infusion, may cause hyperhomocysteinaemia and cobalamin deficiency. Technical complications are specific for each infusion strategy. Formation of subcutaneous nodules is the most common problem with apomorphine infusion. Dislocation of the intestinal tube is the most common problem with levodopa/carbidopa infusion. Both pump treatments may be used for 24-hour infusion in selected patients. The long-term experience is reviewed. To conclude, CDS pump treatments may be successfully used for several years in advanced PD.
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| 28. |
- Cedergren Weber, Gustav, et al.
(författare)
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The Impact of COVID-19 on Parkinson's Disease : A Case-Controlled Registry and Questionnaire Study on Clinical Markers and Patients' Perceptions
- 2023
-
Ingår i: Acta Neurologica Scandinavica. - : John Wiley & Sons. - 0001-6314 .- 1600-0404. ; 2023
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Parkinson's disease (PD) is a neurodegenerative disease with motor and nonmotor symptoms. Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Objectives: To explore how COVID-19 affects motor, nonmotor, and general health aspects of PD and to map how PD patients perceive their change in symptoms since falling ill with COVID-19.Method: The study was descriptive, case-controlled, and based on both registry and questionnaire data. At baseline, the controls were matched on age, sex, and disease severity. Information on the severity of the disease, nonmotor symptoms, motor symptoms, and general health was retrieved from the Swedish Registry for PD. Registry data from a COVID-19 group (n=45) and a control group (n=73), as well as questionnaires from a COVID-19 group (n=24) and a control group (n=42), were compared.Results: We did not find that SARS-CoV-2 infection affects any major aspect of nonmotor symptoms, motor symptoms, general health, and perception of change in PD patients' post-COVID-19. Compared to controls, the COVID-19 group reported a more positive subjective experience of pain and quality of life and a perception of change post-COVID-19 regarding general motor function, sleep quality, and mood (all p<0.05).Conclusion: Although SARS-CoV-2 infection does not seem to affect PD symptoms in any major respect, the subjective experience of several aspects of life in PD patients might be slightly improved post-COVID-19 compared to a control group. The findings warrant further investigations due to the small sample size and possible survivorship bias.
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| 29. |
- Devos, David, et al.
(författare)
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Trial of Deferiprone in Parkinson’s Disease
- 2022
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 387:22, s. 2045-2055
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDIron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson's disease, but its effects on disease progression are unclear.METHODSWe conducted a multicenter, phase 2, randomized, double-blind trial involving participants with newly diagnosed Parkinson's disease who had never received levodopa. Participants were assigned (in a 1:1 ratio) to receive oral deferiprone at a dose of 15 mg per kilogram of body weight twice daily or matched placebo for 36 weeks. Dopaminergic therapy was withheld unless deemed necessary for symptom control. The primary outcome was the change in the total score on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 260, with higher scores indicating more severe impairment) at 36 weeks. Secondary and exploratory clinical outcomes at up to 40 weeks included measures of motor and nonmotor disability. Brain iron content measured with the use of magnetic resonance imaging was also an exploratory outcome.RESULTSA total of 372 participants were enrolled; 186 were assigned to receive deferiprone and 186 to receive placebo. Progression of symptoms led to the initiation of dopaminergic therapy in 22.0% of the participants in the deferiprone group and 2.7% of those in the placebo group. The mean MDS-UPDRS total score at baseline was 34.3 in the deferiprone group and 33.2 in the placebo group and increased (worsened) by 15.6 points and 6.3 points, respectively (difference, 9.3 points; 95% confidence interval, 6.3 to 12.2; P<0.001). Nigrostriatal iron content decreased more in the deferiprone group than in the placebo group. The main serious adverse events with deferiprone were agranulocytosis in 2 participants and neutropenia in 3 participants.CONCLUSIONSIn participants with early Parkinson's disease who had never received levodopa and in whom treatment with dopaminergic medications was not planned, deferiprone was associated with worse scores in measures of parkinsonism than those with placebo over a period of 36 weeks.
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| 30. |
- Drevin, Jennifer, et al.
(författare)
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Patients' views on using human embryonic stem cells to treat Parkinson's disease : an interview study
- 2022
-
Ingår i: BMC Medical Ethics. - : Springer Nature. - 1472-6939. ; 23
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Human embryonic stem cells (hESC) as a source for the development of advanced therapy medicinal products are considered for treatment of Parkinson's disease (PD). Research has shown promising results and opened an avenue of great importance for patients who currently lack a disease modifying therapy. The use of hESC has given rise to moral concerns and been the focus of often heated debates on the moral status of human embryos. Approval for marketing is still pending.Objective: To Investigate the perspectives and concerns of patients with PD, patients being the directly concerned stakeholders in the ethical discussion.Methods: Qualitative semi-structured interviews related to this new therapy in seventeen patients from two Swedish cities.Results: The participants expressed various interests related to the use of human embryos for development of medicinal therapies; however, overall, they were positive towards the use of hESC for treatment of PD. It was deemed important that the donating woman or couple made the choice to donate embryos voluntarily. Furthermore, there were concerns that the industry does not always prioritise the patient over profit; thus, transparency was seen as important.
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| 31. |
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| 32. |
- Fagius, Jan, et al.
(författare)
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Neurologi
- 2012
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Bok (övrigt vetenskapligt/konstnärligt)
|
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| 33. |
- Fagius, Jan, et al.
(författare)
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Neurologisk symtomlära
- 2012
-
Ingår i: Neurologi. - : Liber.
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Bokkapitel (populärvet., debatt m.m.)
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| 34. |
- Fällmar, David, et al.
(författare)
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Imaging features associated with idiopathic normal pressure hydrocephalus have high specificity even when comparing with vascular dementia and atypical parkinsonism
- 2021
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Ingår i: Fluids and Barriers of the CNS. - : BioMed Central (BMC). - 2045-8118. ; 18
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Vascular dementia (VaD) and atypical parkinsonism often present with symptoms that can resemble idiopathic normal pressure hydrocephalus (iNPH) and enlarged cerebral ventricles, and can be challenging differential diagnoses. The aim was to investigate frequencies of imaging features usually associated with iNPH and their radiological diagnostic accuracy in a sample containing the relevant differential diagnoses VaD, progressive supranuclear palsy (PSP), multiple system atrophy parkinsonian type (MSA-P), and healthy controls.Methods: Nine morphological imaging features usually associated with iNPH were retrospectively investigated in MR images of 55 patients with shunt-responsive iNPH, 32 patients with VaD, 30 patients with PSP, 27 patients with MSA-P, and 39 age-matched healthy controls. Logistic regression and receiver operating characteristic curves were used to assess diagnostic accuracy, sensitivity, and specificity for each imaging finding.Results: In a logistic regression model using iNPH diagnosis as a dependent variable, the following imaging features contributed significantly to the model: callosal angle (OR = 0.95 (0.92-0.99), p = 0.012), Evans' index * 100 (OR = 1.51 (1.23-1.86), p < 0.001), enlarged Sylvian fissures (OR = 6.01 (1.42-25.40), p = 0.015), and focally enlarged sulci (OR = 10.18 (1.89-55.02), p = 0.007). Imaging features with 95% specificity for iNPH were: callosal angle <= 71 degrees, temporal horns >= 7 mm, Evans' index >= 0.37, iNPH Radscale >= 9, and presence of DESH, bilateral ventricular roof bulgings or focally enlarged sulci. A simplified version of the iNPH Radscale with only four features resulted in equally high diagnostic accuracy as the original iNPH Radscale.Conclusions: There is a notable overlap between some of the commonly used imaging markers regarding iNPH, VaD and atypical parkinsonism, such as PSP. However, this study shows that the specificity of imaging markers usually associated with iNPH was high even when comparing with these challenging differential diagnoses. The callosal angle was the single imaging feature with highest diagnostic accuracy to discriminate iNPH from its mimics. A simplified rating scale using only a few selected features could be used with retained specificity.
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| 35. |
- Georgiopoulos, Charalampos, et al.
(författare)
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Quantitative brain stem assessment in discriminating neurodegenerative disorders from normal pressure hydrocephalus
-
Ingår i: Journal of Neuroimaging. - 1051-2284.
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: Differentiating idiopathic normal pressure hydrocephalus (iNPH) from neurodegenerative disorders such as progressive supranuclear palsy (PSP), Multiple System Atrophy—parkinsonian type (MSA-P), and vascular dementia (VaD) is challenging due to overlapping clinical and neuroimaging findings. This study assesses if quantitative brain stem and cerebellum metrics can aid in this differentiation. Methods: We retrospectively compared the sagittal midbrain area, midbrain to pons ratio, MR parkinsonism index (MRPI), and cerebellar atrophy in 30 PSP patients, 31 iNPH patients, 27 MSA-P patients, 32 VaD patients, and 25 healthy controls. Statistical analyses determined group differences, sensitivity, specificity, and the area under the receiver operating characteristic curves. Results: There was an overlap in midbrain morphology between PSP and iNPH, as assessed with MRPI, midbrain to pons ratio, and midbrain area. A cutoff value of MRPI > 13 exhibited 84% specificity in distinguishing PSP from iNPH and 100% in discriminating PSP from all other conditions. A cutoff value of midbrain to pons ratio at <0.15 yielded 95% specificity for differentiating PSP from iNPH and 100% from all other conditions. A cutoff value of midbrain area at <87 mm2 exhibited 97% specificity for differentiating PSP from iNPH and 100% from all other conditions. All measures showed low sensitivity. Cerebellar atrophy did not differ significantly among groups. Conclusion: Our study questions MRPI's diagnostic performance in distinguishing PSP from iNPH. Simpler indices such as midbrain to pons ratio and midbrain area showed similar or better accuracy. However, all these indices displayed low sensitivity despite significant differences among PSP, MSA-P, and VaD.
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| 36. |
- Grauman, Åsa, 1982-, et al.
(författare)
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Attitudes and values among the Swedish general public to using human embryonic stem cells for medical treatment
- 2022
-
Ingår i: BMC Medical Ethics. - : Springer Nature. - 1472-6939. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of human embryonic stem cells (ES cells) for the development of medical therapies is surrounded with moral concerns. The aim of this study was to assess the public's attitudes toward the use of ES cells for treatment of Parkinson's disease (PD) and other diseases, what factors are most important to consider when using ES cells for drug development, and if there is an association between religious beliefs and attitudes toward using ES cells for medical treatment.Methods: A randomly selected sample of the Swedish public, aged 18-87-years-old, completed an online survey (n = 467). The survey assessed socio-demographics, religious views, perceived moral status of the embryo, and attitudes toward using ES cells for medical treatment of PD and other diseases. Adjusted odds ratios (ORs) and 95% confidence intervals (CI) for positive vs. negative attitude toward using ES cells for drug development were computed using logistic regression.Results: The respondents were positive about using ES for treatment; specifically, 70% totally agreed that it is acceptable to use ES cells for treatment of PD, while 40% totally agreed that it is acceptable to use ES cells for treatment but induced pluripotent cells is just as efficient. Religion being of little importance in one's life was associated with a positive attitude toward using ES cells for treatment of PD (adjusted OR 6.39, 95% CI 2.78-14.71). The importance of being able "to access new, effective treatments against diseases that do not have any treatment available " was ranked as the most important factor to consider when using ES cells for drug development.Conclusion: Most respondents are positive about using ES cells for drug development, and making effective treatments accessible to those who do not have any. However, these attitudes are influenced by the specific disorder that the drug development is intended for, as well as the religious views and perceived moral status of the early embryo.
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| 37. |
- Gretarsdottir, Helga Maria, et al.
(författare)
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Personalized Medicine Approach in Treating Parkinson's Disease, Using Oral Administration of Levodopa/Carbidopa Microtablets in Clinical Practice
- 2021
-
Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 11:8
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The most effective symptomatic treatment in Parkinson's disease (PD) is levodopa in standard doses. However, as the disease progresses, there may be a need for a more personalized approach and fine tuning, in accordance with the patients' needs. This study aims to evaluate the individual experience of levodopa/carbidopa 5/1.25 mg microtablets (LC-5) in clinical practice with respect to efficacy, tolerability, and usability. The method used was as follows: patients answered a questionnaire concerning the effect and usability of LC-5, and their medical records were reviewed. Regarding results, thirty-five survey responses were obtained, and 29 patients' medical records were reviewed. The LC-5 dose dispenser usability was generally rated positively and facilitated medication adherence. The majority (85%) of patients reported symptom improvement while using LC-5, compared with previous standard treatments. These results suggest that LC-5 therapy is generally well-tolerated, with favorable patient-reported efficacy and user friendliness, as well as the possibility for an individualized, fine-tuned PD treatment. Further studies with a prospective design and larger study population are needed to confirm the results.
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| 38. |
- Herman, Stephanie, et al.
(författare)
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Alterations in the tyrosine and phenylalanine pathways revealed by biochemical profiling in cerebrospinal fluid of Huntington's disease subjects
- 2019
-
Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Huntington's disease (HD) is a severe neurological disease leading to psychiatric symptoms, motor impairment and cognitive decline. The disease is caused by a CAG expansion in the huntingtin (HTT) gene, but how this translates into the clinical phenotype of HD remains elusive. Using liquid chromatography mass spectrometry, we analyzed the metabolome of cerebrospinal fluid (CSF) from premanifest and manifest HD subjects as well as control subjects. Inter-group differences revealed that the tyrosine metabolism, including tyrosine, thyroxine, L-DOPA and dopamine, was significantly altered in manifest compared with premanifest HD. These metabolites demonstrated moderate to strong associations to measures of disease severity and symptoms. Thyroxine and dopamine also correlated with the five year risk of onset in premanifest HD subjects. The phenylalanine and the purine metabolisms were also significantly altered, but associated less to disease severity. Decreased levels of lumichrome were commonly found in mutated HTT carriers and the levels correlated with the five year risk of disease onset in premanifest carriers. These biochemical findings demonstrates that the CSF metabolome can be used to characterize molecular pathogenesis occurring in HD, which may be essential for future development of novel HD therapies.
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| 39. |
- Hultqvist, Jenny, et al.
(författare)
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Everyday Occupations and Other Factors in Relation to Mental Well-Being among Persons with Advanced Parkinson’s Disease
- 2020
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Ingår i: Occupational Therapy in Health Care. - : Informa UK Limited. - 0738-0577 .- 1541-3098. ; 34:1, s. 1-18
-
Tidskriftsartikel (refereegranskat)abstract
- This cross-sectional study investigated performed activities and the level of satisfaction with everyday occupations among people (n = 67) with advanced Parkinson’s disease (PD), and how these factors and experiences of social relationships were related to mental well-being. Managing one’s hygiene and physical exercises were activities that the majority still performed, whereas few were engaged in work or other productive occupations. Perceived health problems and satisfaction with everyday occupations were important factors for mental well-being since satisfaction with everyday occupations may be an important focus for occupational therapists and other health professionals when supporting mental well-being among persons with advanced PD.
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| 40. |
- Jansson, Daniel, et al.
(författare)
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Stochastic anomaly detection in eye-tracking data for quantification of motor symptoms in Parkinson's disease
- 2015
-
Ingår i: Signal and Image Analysis for Biomedical and Life Sciences. - Cham : Springer. - 9783319109831 ; , s. 63-82
-
Bokkapitel (refereegranskat)abstract
- Two methods for distinguishing between healthy controls and patients diagnosed with Parkinson's disease by means of recorded smooth pursuit eye movements are presented and evaluated. Both methods are based on the principles of stochastic anomaly detection and make use of orthogonal series approximation for probability distribution estimation. The first method relies on the identification of a Wiener model of the smooth pursuit system and attempts to find statistically significant differences between the estimated parameters in healthy controls and patients with Parkinson's disease. The second method applies the same statistical method to distinguish between the gaze trajectories of healthy and Parkinson subjects tracking visual stimuli. Both methods show promising results, where healthy controls and patients with Parkinson's disease are effectively separated in terms of the considered metric. The results are preliminary because of the small number of participating test subjects, but they are indicative of the potential of the presented methods as diagnosing or staging tools for Parkinson's disease.
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| 41. |
- Jansson, Daniel, et al.
(författare)
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Stochastic anomaly detection in eye-tracking data for quantification of motor symptoms in Parkinson's disease
- 2013
-
Ingår i: International Symposium on Computational Models for Life Sciences. - Melville, NY : American Institute of Physics (AIP). - 9780735411876 ; , s. 98-107
-
Konferensbidrag (refereegranskat)abstract
- Two methods for distinguishing between healthy controls and patients diagnosed with Parkinson's disease by means of recorded smooth pursuit eye movements are presented and evaluated. Both methods are based on the principles of stochastic anomaly detection and make use of orthogonal series approximation for probability distribution estimation. The first method relies on the identification of a Wiener-type model of the smooth pursuit system and attempts to find statistically significant differences between the estimated parameters in healthy controls and patientts with Parkinson's disease. The second method applies the same statistical method to distinguish between the gaze trajectories of healthy and Parkinson subjects attempting to track visual stimuli. Both methods show promising results, where healthy controls and patients with Parkinson's disease are effectively separated in terms of the considered metric. The results are preliminary because of the small number of participating test subjects, but they are indicative of the potential of the presented methods as diagnosing or staging tools for Parkinson's disease.
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| 42. |
- Johansson, Anders, et al.
(författare)
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Continuous delivery of energy or L-dopa: Identifying advantages and limitations of DBS and levodopa-carbidopa intestinal gel in ansence of head-to-head comparisons
- 2012
-
Ingår i: Basal Ganglia. - : Elsevier BV. - 2210-5336. ; 2:4, s. 221-226
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Tidskriftsartikel (refereegranskat)abstract
- Deep brain stimulation (DBS) and levodopa–carbidopa intestinal gel (LCIG) are invasive, efficacious treatments for advanced Parkinson’s disease, but so far head-to-head comparisons are scarce. Although their indications and improvements in motor outcome and quality of life may be broadly similar, these treatment modalities have different modes of action and side effect profiles. This article summarizes a presentation at the 2nd International Conference on Knowledge Gaps in Parkinson’s Disease and other Movement Disorders in Feburary 2012. An overview of the existing evidence for efficacy and adverse events of LCIG and DBS in short- and long-term is provided. Examples of factors at present affecting choice of treatment are given. The obvious knowledge gap is the need to better identify the appropriate time and place to operate patients with Parkinson’s disease. There are major difficulties facing us when trying to resolve this issue. We argue for a registry of patients exposed to these very efficacious, but expensive and potentially harmful, symptomatic treatments.
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| 43. |
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| 44. |
- Johansson, Dongni, 1988, et al.
(författare)
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Evaluation of a sensor algorithm for motor state rating in Parkinson's disease
- 2019
-
Ingår i: Parkinsonism & Related Disorders. - : Elsevier BV. - 1353-8020 .- 1873-5126. ; 64:July, s. 112-117
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: A treatment response objective index (TRIS) was previously developed based on sensor data from pronation-supination tests. This study aimed to examine the performance of TRIS for medication effects in a new population sample with Parkinson's disease (PD) and its usefulness for constructing individual dose-response models. Methods: Twenty-five patients with PD performed a series of tasks throughout a levodopa challenge while wearing sensors. TRIS was used to determine motor changes in pronation-supination tests following a single levodopa dose, and was compared to clinical ratings including the Treatment Response Scale (TRS) and six sub-items of the UPDRS part III. Results: As expected, correlations between TRIS and clinical ratings were lower in the new population than in the initial study. TRIS was still significantly correlated to TRS (r(s) = 0.23, P < 0.001) with a root mean square error (RMSE) of 1.33. For the patients (n = 17) with a good levodopa response and clear motor fluctuations, a stronger correlation was found (r(s) = 0.38, RMSE = 1.29, P < 0.001). The mean TRIS increased significantly when patients went from the practically defined off to their best on state (P = 0.024). Individual dose-response models could be fitted for more participants when TRIS was used for modelling than when TRS ratings were used. Conclusion: The objective sensor index shows promise for constructing individual dose-response models, but further evaluations and retraining of the TRIS algorithm are desirable to improve its performance and to ensure its clinical effectiveness.
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| 45. |
- Johansson, Dongni, 1988, et al.
(författare)
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Individualization of levodopa treatment using a microtablet dispenser and ambulatory accelerometry
- 2018
-
Ingår i: CNS Neuroscience & Therapeutics. - : Wiley. - 1755-5930 .- 1755-5949. ; 24:5, s. 439-447
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: This 4-week open-label observational study describes the effect of introducing a microtablet dose dispenser and adjusting doses based on objective free-living motor symptom monitoring in individuals with Parkinson's disease (PD). Methods: Twenty-eight outpatients with PD on stable levodopa treatment with dose intervals of ≤4 hour had their daytime doses of levodopa replaced with levodopa/carbidopa microtablets, 5/1.25 mg (LC-5) delivered from a dose dispenser device with programmable reminders. After 2 weeks, doses were adjusted based on ambulatory accelerometry and clinical monitoring. Results: Twenty-four participants completed the study per protocol. The daily levodopa dose was increased by 15% (112 mg, P < 0.001) from period 1 to 2, and the dose interval was reduced by 12% (22 minutes, P = 0.003). The treatment adherence to LC-5 was high in both periods. The MDS-UPDRS parts II and III, disease-specific quality of life (PDQ-8), wearing-off symptoms (WOQ-19), and nonmotor symptoms (NMS Quest) improved after dose titration, but the generic quality-of-life measure EQ-5D-5L did not. Blinded expert evaluation of accelerometry results demonstrated improvement in 60% of subjects and worsening in 25%. Conclusions: The introduction of a levodopa microtablet dispenser and accelerometry aided dose adjustments improve PD symptoms and quality of life in the short term.
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| 46. |
- Jonasson, My, et al.
(författare)
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Development of a clinically feasible [11C]PE2I PET method for differential diagnosis of parkinsonism using reduced scan duration and automated reference region extraction.
- 2017
-
Ingår i: American Journal of Nuclear Medicine and Molecular Imaging. - 2160-8407. ; 7:6, s. 263-274
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Tidskriftsartikel (refereegranskat)abstract
- [11C]PE2I is a highly selective dopamine transporter PET ligand. Parametric images based on dynamic [11C]PE2I scans, showing dopamine transporter availability (BPND) and relative cerebral blood flow (R1), can be used in differential diagnosis of parkinsonism. This work aimed to investigate a shortened scan duration and automated generation of parametric images which are two prerequisites for routine clinical application. Twelve subjects with parkinsonism and seventeen healthy controls underwent 80 min dynamic [11C]PE2I PET scans. BPND and R1 images were generated using cerebellum reference region defined on a co-registered MRI, as well as a supervised cluster analysis (SVCA)-based reference. Initial 20, 30 and 40 min of the scans were extracted and images of standardized uptake value ratio (SUVR) and R1 were computed using MRI- and SVCA-based reference. Correlation was high between striatal 80 min MRI-based BPND and 40 min SVCA-based SUVR-1 (R2=0.95). High correlation was also found between R1 values in striatal and limbic regions (R2≥0.91) whereas correlation was moderate for cortical regions (R2=0.71). The results indicate that dynamic [11C]PE2I scans can be restricted to 40 min and that SVCA can be used for automatic extraction of a reference region. These outcomes will support routine applications of [11C]PE2I PET in clinical settings.
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| 47. |
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| 48. |
- Jonasson, My, et al.
(författare)
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Validation of parametric methods for [(11)C]PE2I positron emission tomography
- 2013
-
Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 74, s. 172-178
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVESThe radioligand [(11)C]PE2I is highly selective for dopamine transporter (DAT) and can be used in vivo for investigation of changes in DAT concentration, progression of disease and validation of treatment using positron emission tomography (PET). DAT is an important protein for regulation of central dopamine concentration and DAT deficiency has been associated with several neurodegenerative and neuropsychiatric disorders. Accurate parametric images are a prerequisite for clinical application of [(11)C]PE2I. The purpose of this study was to evaluate different methods for producing [(11)C]PE2I parametric images, showing binding potential (BPND) and relative delivery (R1) at the voxel level, using clinical data as well as simulations.METHODSInvestigations were made in twelve subjects either with social anxiety disorder (n=6) or parkinsonian syndrome (n=6), each receiving an 80min dynamic PET scan. All subjects underwent a T1-weighted MRI scan which was co-registered to the PET images and used for definition of regions of interest using a probabilistic template (PVElab). Two basis function implementations (receptor parametric mapping: RPM, RPM2) of the simplified reference tissue model (SRTM) and three multilinear reference tissue models (MRTMo, MRTM and MRTM2) were used for computation of parametric BPND and R1 images. In addition, reference Logan and standard uptake value ratio (SUVr) were investigated. Evaluations of BPND and R1 images were performed using linear regression to compare the parametric methods to region-based analyses with SRTM and cerebellar gray matter as reference region. Accuracy and precision of each method were assessed by simulations.RESULTSCorrelation and slope of linear regression between parametric and region-based BPND and R1 values in both striatum and extra-striatal regions were optimal for RPM (R(2)=0.99 for both BPND and R1; slopes 0.99 and 0.98 for BPND and R1, respectively, in striatum). In addition, accuracy and precision were best for RPM and RPM2.CONCLUSIONThe basis function methods provided more robust estimations of the parameters compared to the other models and performed best in simulations. RPM, a basis function implementation of SRTM, is the preferred method for voxel level analysis of [(11)C]PE2I PET studies.
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| 49. |
- Jusufi, Ilir, 1983-, et al.
(författare)
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TapVis : A Data Visualization Approach for Assessment of Alternating Tapping Performance in Patients with Parkinson's Disease
- 2018
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Ingår i: EuroVis 2018 - Short Papers. - : Eurographics - European Association for Computer Graphics. - 9783038680604 ; , s. 55-59
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Konferensbidrag (refereegranskat)abstract
- Advancements in telemedicine have been helpful for frequent monitoring of patients with Parkinson's disease (PD) from remote locations and assessment of their individual symptoms and treatment-related complications. These data can be useful for helping clinicians to interpret symptom states and individually tailor the treatments by visualizing the physiological information collected by sensor-based systems. In this paper we present a visualization metaphor that represents symptom information of PD patients during tapping tests performed with a smartphone. The metaphor has been developed and evaluated with a clinician. It enabled the clinician to observe fine motor impairments and identify motor fluctuations regarding several movement aspects of patients that perform the tests from their homes.
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| 50. |
- Jusufi, Ilir, et al.
(författare)
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Visualization of spiral drawing data of patients with Parkinson's disease
- 2014
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Ingår i: IEEE International Conference on Information Visualization. - : IEEE Press. - 9781479941032 ; , s. 346-350, s. 346-350, s. 346-350
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Konferensbidrag (refereegranskat)abstract
- Patients with Parkinson's disease (PD) need to be frequently monitored in order to assess their individual symptoms and treatment-related complications. Advances in technology have introduced telemedicine for patients in remote locations. However, data produced in such settings lack much information and are not easy to analyze or interpret compared to traditional, direct contact between the patient and clinician. Therefore, there is a need to present the data using visualization techniques in order to communicate in an understandable and objective manner to the clinician. This paper presents interaction and visualization approaches used to aid clinicians in the analysis of repeated measures of spirography of PD patients gathered by means of a telemetry touch screen device. The proposed approach enables clinicians to observe fine motor impairments and identify motor fluctuations of their patients while they perform the tests from their homes using the telemetry device.
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