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- 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
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Ingår i: Acta Neurologica Scandinavica. - : John Wiley & Sons. - 0001-6314 .- 1600-0404. ; 2023
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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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| 3. |
- 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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| 4. |
- Senek, Marina, et al.
(författare)
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Levodopa/carbidopa microtablets in Parkinson's disease : a study of pharmacokinetics and blinded motor assessment
- 2017
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Ingår i: European Journal of Clinical Pharmacology. - Heidelberg, Germany : Springer. - 0031-6970 .- 1432-1041 .- 0014-2999. ; 73:5, s. 563-571
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Tidskriftsartikel (refereegranskat)abstract
- Background: Motor function assessments with rating scales in relation to the pharmacokinetics of levodopa may increase the understanding of how to individualize and fine-tune treatments.Objectives: This study aimed to investigate the pharmacokinetic profiles of levodopa-carbidopa and the motor function following a single-dose microtablet administration in Parkinson’s disease.Methods: This was a single-center, open-label, single-dose study in 19 patients experiencing motor fluctuations. Patients received 150% of their individual levodopa equivalent morning dose in levodopa-carbidopa microtablets. Blood samples were collected at pre-specified time points. Patients were video recorded and motor function was assessed with six UPDRS part III motor items, dyskinesia score, and the treatment response scale (TRS), rated by three blinded movement disorder specialists.Results: AUC0–4/dose and Cmax/dose for levodopa was found to be higher in Parkinson’s disease patients compared with healthy subjects from a previous study, (p = 0.0008 and p = 0.026, respectively). The mean time to maximum improvement in sum of six UPDRS items score was 78 min (±59) (n = 16), and the mean time to TRS score maximum effect was 54 min (±51) (n = 15). Mean time to onset of dyskinesia was 41 min (±38) (n = 13).Conclusions: In the PD population, following levodopa/carbidopa microtablet administration in fasting state, the Cmax and AUC0–4/dose were found to be higher compared with results from a previous study in young, healthy subjects. A large between subject variability in response and duration of effect was observed, highlighting the importance of a continuous and individual assessment of motor function in order to optimize treatment effect.
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| 5. |
- Thomas, Ilias, et al.
(författare)
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Sensor-based algorithmic dosing suggestions for oral administration of levodopa/carbidopa microtablets for Parkinson's disease : a first experience
- 2019
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 266:3, s. 651-658
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Dosing schedules for oral levodopa in advanced stages of Parkinson's disease (PD) require careful tailoring to fit the needs of each patient. This study proposes a dosing algorithm for oral administration of levodopa and evaluates its integration into a sensor-based dosing system (SBDS).MATERIALS AND METHODS: In collaboration with two movement disorder experts a knowledge-driven, simulation based algorithm was designed and integrated into a SBDS. The SBDS uses data from wearable sensors to fit individual patient models, which are then used as input to the dosing algorithm. To access the feasibility of using the SBDS in clinical practice its performance was evaluated during a clinical experiment where dosing optimization of oral levodopa was explored. The supervising neurologist made dosing adjustments based on data from the Parkinson's KinetiGraph™ (PKG) that the patients wore for a week in a free living setting. The dosing suggestions of the SBDS were compared with the PKG-guided adjustments.RESULTS: The SBDS maintenance and morning dosing suggestions had a Pearson's correlation of 0.80 and 0.95 (with mean relative errors of 21% and 12.5%), to the PKG-guided dosing adjustments. Paired t test indicated no statistical differences between the algorithmic suggestions and the clinician's adjustments.CONCLUSION: This study shows that it is possible to use algorithmic sensor-based dosing adjustments to optimize treatment with oral medication for PD patients.
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| 7. |
- 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. - : WILEY. - 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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| 8. |
- 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
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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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| 9. |
- Rystedt, Alma, 1980-
(författare)
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Botulinum Toxin : Formulation, Concentration and Treatment
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Botulinum toxin (BTX) is used in various fields of medicine, including the treatment of hyperhidrosis and cervical dystonia. Botox®, Dysport®, Xeomin® and NeuroBloc® are commercially available BTX products, which are formulated differently and their dosing units are unique. Dosage and concentration of the prepared solution for injection varies considerably among studies comparing the products. Improved guidelines on concentration and dosing when changing from one product to another are warranted. This would ensure the use of the lowest effective doses for good effect, minimal risk of antibody formation and side-effects as well as reduced costs.The aim of the present work was to find the most appropriate BTX concentration for each of the four products to achieve the highest sweat reducing effect and to investigate dose conversion ratios between Botox and Dysport in the treatment of cervical dystonia when the products are diluted to the same concentration, 100 U/ml.Paper I and II clearly confirm that it is crucial to consider the BTX concentration in a treatment regimen, especially when changing between different products. The optimal concentration to reduce sweating varies among the products and was found to be 25 U/ml for Botox and Xeomin, approximately 100 U/ml for Dysport and 50 U/ml for NeuroBloc. However, for NeuroBloc the optimal concentration might be even lower.In Paper III, which is a retrospective study using casebook notes from 75 patients with cervical dystonia, it was found that the most appropriate dose conversion ratio to use when switching from Botox to Dysport was 1:1.7.In Paper IV, Botox and Dysport were prospectively compared in a double-blind, randomized clinical trial in two different dose conversion ratios (1:3 and 1:1.7) when diluted to the same concentration (100 U/ml). No statistically significant difference was seen between Botox (1:3) and Dysport nor between Botox (1:1.7) and Dysport four weeks after treatment. Some of the secondary outcome observations, however, did indicate that the ratio 1:3 resulted in suboptimal efficacy of Botox but this must be further validated in a larger patient material.
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| 10. |
- Sousa, João M., et al.
(författare)
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Accuracy and precision of zero-echo-time, single- and multi-atlas attenuation correction for dynamic [11C]PE2I PET-MR brain imaging
- 2020
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Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A valid photon attenuation correction (AC) method is instrumental for obtaining quantitatively correct PET images. Integrated PET/MR systems provide no direct information on attenuation, and novel methods for MR-based AC (MRAC) are still under investigation. Evaluations of various AC methods have mainly focused on static brain PET acquisitions. In this study, we determined the validity of three MRAC methods in a dynamic PET/MR study of the brain.METHODS: Nine participants underwent dynamic brain PET/MR scanning using the dopamine transporter radioligand [11C]PE2I. Three MRAC methods were evaluated: single-atlas (Atlas), multi-atlas (MaxProb) and zero-echo-time (ZTE). The 68Ge-transmission data from a previous stand-alone PET scan was used as reference method. Parametric relative delivery (R1) images and binding potential (BPND) maps were generated using cerebellar grey matter as reference region. Evaluation was based on bias in MRAC maps, accuracy and precision of [11C]PE2I BPND and R1 estimates, and [11C]PE2I time-activity curves. BPND was examined for striatal regions and R1 in clusters of regions across the brain.RESULTS: For BPND, ZTE-MRAC showed the highest accuracy (bias < 2%) in striatal regions. Atlas-MRAC exhibited a significant bias in caudate nucleus (- 12%) while MaxProb-MRAC revealed a substantial, non-significant bias in the putamen (9%). R1 estimates had a marginal bias for all MRAC methods (- 1.0-3.2%). MaxProb-MRAC showed the largest intersubject variability for both R1 and BPND. Standardized uptake values (SUV) of striatal regions displayed the strongest average bias for ZTE-MRAC (~ 10%), although constant over time and with the smallest intersubject variability. Atlas-MRAC had highest variation in bias over time (+10 to - 10%), followed by MaxProb-MRAC (+5 to - 5%), but MaxProb showed the lowest mean bias. For the cerebellum, MaxProb-MRAC showed the highest variability while bias was constant over time for Atlas- and ZTE-MRAC.CONCLUSIONS: Both Maxprob- and ZTE-MRAC performed better than Atlas-MRAC when using a 68Ge transmission scan as reference method. Overall, ZTE-MRAC showed the highest precision and accuracy in outcome parameters of dynamic [11C]PE2I PET analysis with use of kinetic modelling.
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