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  • 1. Aghanavesi, S
    et al.
    Bergquist, F
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Senek, Marina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Memedi, M
    Motion Sensor-Based Assessment of Parkinson's Disease Motor Symptoms During Leg Agility Tests: Results From Levodopa Challenge2020In: IEEE journal of biomedical and health informatics, ISSN 2168-2194, E-ISSN 2168-2208, Vol. 24, no 1, p. 111-119Article in journal (Refereed)
    Abstract [en]

    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 ten-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.

  • 2.
    Aghanavesi, Somayeh
    et al.
    Dalarna Univ, Falun, Sweden.
    Memedi, Mevludin
    Örebro Univ, Örebro, Sweden.
    Dougherty, Mark
    Dalarna Univ, Falun, Sweden.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Westin, Jerker
    Dalarna Univ, Falun, Sweden.
    Verification of a Method for Measuring Parkinson's Disease Related Temporal Irregularity in Spiral Drawings2017In: Sensors, E-ISSN 1424-8220, Vol. 17, no 10, article id 2431Article in journal (Refereed)
    Abstract [en]

    -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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  • 3.
    Aghanavesi, Somayeh
    et al.
    Dalarna Univ, Dept Comp Engn, Falun, Sweden..
    Westin, Jerker
    Dalarna Univ, Dept Comp Engn, Falun, Sweden..
    Bergquist, Filip
    Univ Gothenburg, Dept Pharmacol, Inst Neurosci & Physiol, Gothenburg, Sweden..
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Aquilonius, Sten-Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Constantinescu, Radu
    Univ Gothenburg, Dept Clin Neurosci, Gothenburg, Sweden..
    Medvedev, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Automatic control. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Systems and Control.
    Spira, Jack
    Sensidose AB, Sollentuna, Sweden..
    Ohlsson, Fredrik
    Chalmers Univ, Gothenburg, Sweden..
    Thomas, Ilias
    Dalarna Univ, Dept Stat, Falun, Sweden..
    Ericsson, Anders
    Irisity AB, Gothenburg, Sweden..
    Buvarp, Dongni Johansson
    Univ Gothenburg, Dept Clin Neurosci & Rehabil, Gothenburg, Sweden..
    Memedi, Mevludin
    Orebro Univ, Informat, Orebro, Sweden..
    A multiple motion sensors index for motor state quantification in Parkinson's disease2020In: Computer Methods and Programs in Biomedicine, ISSN 0169-2607, E-ISSN 1872-7565, Vol. 189, article id 105309Article in journal (Refereed)
    Abstract [en]

    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.

  • 4.
    Appel, Lieuwe
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Jonasson, My
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Use of C-11-PE2I PET in Differential Diagnosis of Parkinsonian Disorders2015In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 56, no 2, p. 234-242Article in journal (Refereed)
    Abstract [en]

    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.

  • 5.
    Aquilonius, Sten-Magnus
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. neurologi.
    Boman, Gunnar
    Department of Medical Sciences.
    Nyholm, Dag
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. neurologi.
    Från Alzheimer till övervikt2007Book (Other (popular scientific, debate etc.))
  • 6.
    Aquilonius, Sten-Magnus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Development of new levodopa treatment strategies in Parkinson’s disease – from bedside to bench to bedside2017In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, no 2, p. 71-77Article, review/survey (Refereed)
    Abstract [en]

    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'.

  • 7.
    Bergquist, Filip
    et al.
    Univ Gothenburg, Dept Pharmacol, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Neurol, Gothenburg, Sweden..
    Ehrnebo, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Pharm Assist Sweden AB, Uppsala, Sweden..
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurovetenskap.
    Johansson, Anders
    Karolinska Inst, Dept Clin Neurosci, Solna, Sweden..
    Lundin, Fredrik
    Linköping Univ, Dept Biomed & Clin Sci, Linköping, Sweden..
    Odin, Per
    Lund Univ, Dept Clin Sci, Neurol, Lund, Sweden..
    Svenningsson, Per
    Karolinska Inst, Dept Clin Neurosci, Solna, Sweden..
    Hansson, Fredrik
    CTC Clin Trial Consultants AB, Uppsala, Sweden..
    Bring, Leif
    Dizlin Pharmaceut, Gothenburg, Sweden..
    Eriksson, Elias
    Univ Gothenburg, Dept Pharmacol, Gothenburg, Sweden..
    Dizdar, Nil
    Linköping Univ, Dept Biomed & Clin Sci, Linköping, Sweden..
    Pharmacokinetics of Intravenously (DIZ101), Subcutaneously (DIZ102), and Intestinally (LCIG) Infused Levodopa in Advanced Parkinson Disease2022In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 99, no 10, p. E965-E976Article in journal (Refereed)
    Abstract [en]

    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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  • 8. Bergquist, Filip
    et al.
    Johansson, Anders
    Dizdar, Nil
    Widner, Håkan
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Odin, Per
    Svenningsson, Per
    Parkinson's disease - heterogeneous and complex in its clinical presentation.2020In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 117, article id FWEDArticle in journal (Refereed)
    Abstract [sv]

    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.

  • 9. Bergquist, Filip
    et al.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Rörelsestörningar2020In: Neurologi / [ed] Nyholm, Burman, Liber, 2020Chapter in book (Other academic)
  • 10.
    Braun, Madelen
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurovetenskap.
    Bjurnemark, Caroline
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Seo, Woosung
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Freyhult, Eva
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurovetenskap.
    Niemelä, Valter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurovetenskap.
    Blennow, K.
    Zetterberg, H.
    Fällmar, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kultima, Kim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Virhammar, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurovetenskap.
    Higher levels of neurofilament light chain and total tau in CSF are associated with negative outcome after shunt surgery in patients with normal pressure hydrocephalus2022In: Fluids and Barriers of the CNS, E-ISSN 2045-8118, Vol. 19, no 1Article in journal (Refereed)
    Abstract [en]

    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 (Aβ1-42) 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.

    Result: Higher levels of NfL and T-tau were associated with less improvement after shunt surgery (β = − 3.10, p = 0.016 and β = − 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 Aβ1-42 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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  • 11.
    Braun, Madelen
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology.
    Boström, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Molecular Geriatrics.
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Molecular Geriatrics. Univ Hlth Network, Krembil Brain Inst, Toronto, ON, Canada.;Univ Toronto, Dept Med, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON, Canada.;Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada..
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Molecular Geriatrics.
    Löwenmark, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Molecular Geriatrics.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology.
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology.
    Niemelä, Valter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology.
    Freyhult, Eva
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics.
    Kultima, Kim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Virhammar, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology.
    Levels of inflammatory cytokines MCP-1, CCL4, and PD-L1 in CSF differentiate idiopathic normal pressure hydrocephalus from neurodegenerative diseases2023In: Fluids and Barriers of the CNS, E-ISSN 2045-8118, Vol. 20, article id 72Article in journal (Refereed)
    Abstract [en]

    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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  • 12.
    Bredenberg, Susanne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Aquilonius, Sten-Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Nyström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    An automatic dose dispenser for microtablets: A new concept for individual dosage of drugs in tablet form2003In: International Journal of Pharmaceutics, ISSN 0378-5173, Vol. 261, no 1-2, p. 137-146Article in journal (Refereed)
    Abstract [en]

    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.

  • 13.
    Burman, Joachim
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Fagius, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Den neurologiska konsultationen2020In: Neurologi / [ed] Nyholm, Burman, Liber, 2020Chapter in book (Other academic)
    Abstract [sv]

    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. 

  • 14.
    Burman, Joachim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Fagius, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Neurologisk symtomlära2020In: Neurologi, Liber, 2020Chapter in book (Other academic)
  • 15.
    Busk, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Johansson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Long-term efficacy and safety with continuous dopaminergic stimulation pump treatments in Parkinson's disease2011In: European Neurological Review, ISSN 1758-3837, Vol. 6, no 3, p. 156-160Article in journal (Refereed)
    Abstract [en]

    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.

  • 16.
    Busk, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Long-term 24-h levodopa/carbidopa gel infusion in Parkinson's disease2012In: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 18, no 8, p. 1000-1001Article in journal (Refereed)
  • 17. Devos, David
    et al.
    Labreuche, Julien
    Rascol, Olivier
    Corvol, Jean-Christophe
    Duhamel, Alain
    Guyon Delannoy, Pauline
    Poewe, Werner
    Compta, Yaroslau
    Pavese, Nicola
    Růžička, Evžen
    Dušek, Petr
    Post, Bart
    Bloem, Bastiaan R.
    Berg, Daniela
    Maetzler, Walter
    Otto, Markus
    Habert, Marie-Odile
    Lehericy, Stéphane
    Ferreira, Joaquim
    Dodel, Richard
    Tranchant, Christine
    Eusebio, Alexandre
    Thobois, Stéphane
    Marques, Ana-Raquel
    Meissner, Wassilios G.
    Ory-Magne, Fabienne
    Walter, Uwe
    de Bie, Rob M.A.
    Gago, Miguel
    Vilas, Dolores
    Kulisevsky, Jaime
    Januario, Cristina
    Coelho, Miguel V.S.
    Behnke, Stefanie
    Worth, Paul
    Seppi, Klaus
    Ouk, Thavarak
    Potey, Camille
    Leclercq, Céline
    Viard, Romain
    Kuchcinski, Gregory
    Lopes, Renaud
    Pruvo, Jean-Pierre
    Pigny, Pascal
    Garçon, Guillaume
    Simonin, Ophélie
    Carpentier, Jessica
    Rolland, Anne-Sophie
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology.
    Scherfler, Christoph
    Mangin, Jean-François
    Chupin, Marie
    Bordet, Régis
    Dexter, David T.
    Fradette, Caroline
    Spino, Michael
    Tricta, Fernando
    Ayton, Scott
    Bush, Ashley I.
    Devedjian, Jean-Christophe
    Duce, James A.
    Cabantchik, Ioav
    Defebvre, Luc
    Deplanque, Dominique
    Moreau, Caroline
    Trial of Deferiprone in Parkinson’s Disease2022In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 387, no 22, p. 2045-2055Article in journal (Refereed)
    Abstract [en]

    BACKGROUND

    Iron 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.

    METHODS

    We 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.

    RESULTS

    A 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.

    CONCLUSIONS

    In 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.

  • 18.
    Donadio, Vincenzo
    et al.
    IRCCS Ist Sci Neurol Bologna, UOC Clin Neurol, Bologna, Italy.;IRCCS Ist Sci Neurol Bologna, UOC Clin Neurol, Via Altura 3, I-40139 Bologna, Italy..
    Incensi, Alex
    IRCCS Ist Sci Neurol Bologna, UOC Clin Neurol, Bologna, Italy..
    Rizzo, Giovanni
    IRCCS Ist Sci Neurol Bologna, UOC Clin Neurol, Bologna, Italy..
    Westermark, Gunilla T.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Devigili, Grazia
    Fdn IRCCS Ist Neurol Carlo Besta, Milan, Italy..
    De Micco, Rosa
    Univ Campania Luigi Vanvitelli, Dipartimento Sci Med & Chirurg Avanzate, Naples, Italy..
    Tessitore, Alessandro
    Univ Campania Luigi Vanvitelli, Dipartimento Sci Med & Chirurg Avanzate, Naples, Italy..
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology.
    Parisini, Sara
    IRCCS Ist Sci Neurol Bologna, UOC Clin Neurol, Bologna, Italy..
    Nyman, Dag
    Tedeschi, Gioacchino
    Univ Campania Luigi Vanvitelli, Dipartimento Sci Med & Chirurg Avanzate, Naples, Italy..
    Eleopra, Roberto
    Fdn IRCCS Ist Neurol Carlo Besta, Milan, Italy..
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Univ Hlth Network, Krembil Brain Inst, Toronto, ON, Canada; Univ Toronto, Dept Med, Toronto, ON, Canada; Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON, Canada.
    Liguori, Rocco
    IRCCS Ist Sci Neurol Bologna, UOC Clin Neurol, Bologna, Italy..
    Phosphorylated α-synuclein in skin Schwann cells: a new biomarker for multiple system atrophy2023In: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 146, no 3, p. 1065-1074Article in journal (Refereed)
    Abstract [en]

    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.

  • 19.
    Drevin, Jennifer
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology.
    Widner, Håkan
    Skane Univ Hosp, Neurol Clin, S-22185 Lund, Sweden..
    Van Vliet, Trinette
    Skane Univ Hosp, Neurol Clin, S-22185 Lund, Sweden..
    Viberg Johansson, Jennifer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics. Inst Future Studies, Hollandargatan 13, S-11136 Stockholm, Sweden..
    Jiltsova, Elena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology.
    Hansson, Mats G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Patients' views on using human embryonic stem cells to treat Parkinson's disease: an interview study2022In: BMC Medical Ethics, ISSN 1472-6939, E-ISSN 1472-6939, Vol. 23, article id 102Article in journal (Refereed)
    Abstract [en]

    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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  • 20.
    Fagius, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Neurologi2012Book (Other academic)
  • 21.
    Fagius, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Neurologisk symtomlära2012In: Neurologi / [ed] Fagius J, Nyholm D, Liber, 2012Chapter in book (Other (popular science, discussion, etc.))
  • 22.
    Fagius, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Aquilonius, Sten-Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Den neurologiska undersökningen2012In: Neurologi / [ed] Fagius J, Nyholm D, Liber, 2012Chapter in book (Other (popular science, discussion, etc.))
  • 23.
    Fällmar, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Andersson, Oliver
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Löwenmark, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Virhammar, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Imaging features associated with idiopathic normal pressure hydrocephalus have high specificity even when comparing with vascular dementia and atypical parkinsonism2021In: Fluids and Barriers of the CNS, E-ISSN 2045-8118, Vol. 18, article id 35Article in journal (Refereed)
    Abstract [en]

    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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  • 24.
    Grauman, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Hansson, Mats G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology.
    Jiltsova, Elena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology.
    Widner, Håkan
    van Vliet, Trinette
    Drevin, Jennifer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Attitudes and values among the Swedish general public to using human embryonic stem cells for medical treatment2022In: BMC Medical Ethics, ISSN 1472-6939, E-ISSN 1472-6939, Vol. 23, no 1, article id 138Article in journal (Refereed)
    Abstract [en]

    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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  • 25.
    Gretarsdottir, Helga Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Widman, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Johansson, Anders
    Karolinska Inst, Dept Clin Neurosci, S-17177 Stockholm, Sweden..
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Personalized Medicine Approach in Treating Parkinson's Disease, Using Oral Administration of Levodopa/Carbidopa Microtablets in Clinical Practice2021In: Journal of Personalized Medicine, E-ISSN 2075-4426, Vol. 11, no 8, article id 720Article in journal (Refereed)
    Abstract [en]

    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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  • 26.
    Herman, Stephanie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Niemelä, Valter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Emami Khoonsari, Payam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Sundblom, Jimmy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Landtblom, Anne-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Spjuth, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Kultima, Kim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Alterations in the tyrosine and phenylalanine pathways revealed by biochemical profiling in cerebrospinal fluid of Huntington's disease subjects2019In: Scientific Reports, E-ISSN 2045-2322, Vol. 9, article id 4129Article in journal (Refereed)
    Abstract [en]

    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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  • 27. Hultqvist, J
    et al.
    Sahlstrom, T
    Timpka, J
    Henriksen, T
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Odin, P
    Eklund, M
    Everyday Occupations and Other Factors in Relation to Mental Well-Being Among Persons With Advanced Parkinson's Disease2020In: Occupational Therapy in Health Care, ISSN 0738-0577, E-ISSN 1541-3098, Vol. 34, no 1, p. 1-18Article in journal (Refereed)
    Abstract [en]

    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.

  • 28.
    Ilias, Thomas
    et al.
    Dalarna Univ, S-79131 Falun, Sweden..
    Filip, Bergquist
    Gothenburg Univ, S-40530 Gothenburg, Sweden..
    Radu, Constantinescu
    Gothenburg Univ, S-40530 Gothenburg, Sweden..
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Senek, Marina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Mevludin, Memedi
    Dalarna Univ, S-70281 Orebro, Sweden.;Orebro Univ, S-70281 Orebro, Sweden..
    Using measurements from wearable sensors for automatic scoring of Parkinson's disease motor states: results from 7 patients2017In: 2017 39th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), IEEE , 2017, p. 131-134Conference paper (Refereed)
    Abstract [en]

    The objective of this study was to investigate the validity of an objective gait measure for assessment of different motor states of advanced Parkinson's disease (PD) patients. Seven PD patients performed a gait task up to 15 times while wearing sensors on their upper and lower limbs. Each task was performed at specific points during a test day, following a single dose of levodopa-carbidopa. At the time of the tasks the patients were video recorded and three movement disorder experts rated their motor function on three clinical scales: a treatment response scale (TRS) that ranged from -3 (very bradykinetic) to 0 (ON) to +3 (very dyskinetic), a dyskinesia score that ranged from 0 (no dyskinesia) to 4 (extreme dyskinesia), and a bradykinesia score that ranged from 0 (no bradykinesia) to 4 (extreme bradykinesia). Raw accelerometer and gyroscope data of the sensors were processed and analyzed with time series analysis methods to extract features. The utilized features quantified separate limb movements as well as movement symmetries between the limbs. The features were processed with principal component analysis and the components were used as predictors for separate support vector machine (SVM) models for each of the three scales. The performance of each model was evaluated in a leave-one-patient out setting where the observations of a single patient were used as the testing set and the observations of the other 6 patients as the training set. Root mean square error (RMSE) and correlation coefficients for the predictions showed a good ability of the models to map the sensor data into the rating scales. There were strong correlations between the SVM models and the mean ratings of TRS (0.79; RMSE=0.70), bradykinesia score (0.79; RMSE=0.47), and bradykinesia score (0.78; RMSE=0.46). The results presented in this paper indicate that the use of wearable sensors when performing gait tasks can generate measurements that have a good correlation to subjective expert assessments.

  • 29.
    Jansson, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Systems and Control. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Automatic control.
    Medvedev, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Systems and Control. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Automatic control.
    Axelson, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Stochastic anomaly detection in eye-tracking data for quantification of motor symptoms in Parkinson's disease2015In: Signal and Image Analysis for Biomedical and Life Sciences, Springer, 2015, p. 63-82Chapter in book (Refereed)
    Abstract [en]

    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.

  • 30.
    Jansson, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Systems and Control. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Automatic control.
    Medvedev, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Systems and Control. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Automatic control.
    Axelson, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Stochastic anomaly detection in eye-tracking data for quantification of motor symptoms in Parkinson's disease2013In: International Symposium on Computational Models for Life Sciences: CMLS 2013, Melville, NY: American Institute of Physics (AIP), 2013, p. 98-107Conference paper (Refereed)
    Abstract [en]

    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.

  • 31.
    Johansson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Continuous delivery of energy or L-dopa: Identifying advantages and limitations of DBS and levodopa-carbidopa intestinal gel in ansence of head-to-head comparisons2012In: Basal Ganglia, Vol. 2, no 4, p. 221-226Article in journal (Refereed)
    Abstract [en]

    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.

  • 32. Johansson, Dongni
    et al.
    Ericsson, Anders
    Johansson, Anders
    Medvedev, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Systems and Control. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Automatic control.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Ohlsson, Fredrik
    Senek, Marina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Spira, Jack
    Thomas, Ilias
    Westin, Jerker
    Bergquist, Filip
    Individualization of levodopa treatment using a microtablet dispenser and ambulatory accelerometry2018In: CNS Neuroscience & Therapeutics, ISSN 1755-5930, E-ISSN 1755-5949, Vol. 24, no 5, p. 439-447Article in journal (Refereed)
  • 33.
    Johansson, Dongni
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Clin Neurosci, Gothenburg, Sweden.
    Thomas, Ilias
    Dalarna Univ, Dept Microdata Anal, Falun, Sweden.
    Ericsson, Anders
    RISE Acreo, Gothenburg, Sweden;Karolinska Inst, Dept Clin Neurosci, Neurol, Stockholm, Sweden.
    Johansson, Anders
    Medvedev, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Automatic control. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Systems and Control.
    Memedi, Mevludin
    Orebro Univ, Sch Business, Informat, Orebro, Sweden.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Ohlsson, Fredrik
    RISE Acreo, Gothenburg, Sweden.
    Senek, Marina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Spira, Jack
    Sensidose AB, Sollentuna, Sweden.
    Westin, Jerker
    Dalarna Univ, Dept Microdata Anal, Falun, Sweden.
    Bergquist, Filip
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Clin Neurosci, Gothenburg, Sweden;Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Pharmacol, Gothenburg, Sweden.
    Evaluation of a sensor algorithm for motor state rating in Parkinson's disease2019In: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 64, p. 112-117Article in journal (Refereed)
    Abstract [en]

    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.

  • 34.
    Jonasson, My
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Frick, Andreas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Development of a clinically feasible [11C]PE2I PET method for differential diagnosis of parkinsonism using reduced scan duration and automated reference region extraction.2017In: American Journal of Nuclear Medicine and Molecular Imaging, ISSN 2160-8407, Vol. 7, no 6, p. 263-274Article in journal (Refereed)
    Abstract [en]

    [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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  • 35.
    Jonasson, My
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Frick, Andreas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Parametric methods for [11C]PE2I positron emission tomography2012In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 32, no S1, p. S155-S155Article in journal (Other academic)
  • 36.
    Jonasson, My
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Frick, Andreas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Validation of parametric methods for [(11)C]PE2I positron emission tomography2013In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 74, p. 172-178Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES

    The 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.

    METHODS

    Investigations 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.

    RESULTS

    Correlation 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.

    CONCLUSION

    The 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.

  • 37.
    Jusufi, Ilir
    et al.
    Univ Calif Davis, Dept Comp Sci, Davis, CA 95616 USA..
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Memedi, Mevludin
    Dalarna Univ, Sch Technol & Business Studies, Comp Engn, Borlange, Sweden..
    Visualization of spiral drawing data of patients with Parkinson's disease2014In: 2014 18Th International Conference On Information Visualisation (IV), 2014, p. 346-350Conference paper (Refereed)
    Abstract [en]

    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.

  • 38.
    Karni, Liran
    et al.
    Örebro Univ, Ctr Empir Res Informat Syst, Sch Business, Fakultetsgatan 1, S-70281 Örebro, Sweden..
    Jusufi, Ilir
    Linnaeus Univ, Dept Comp Sci & Media Technol, Växjö, Sweden..
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology.
    Klein, Gunnar Oskar
    Örebro Univ, Ctr Empir Res Informat Syst, Sch Business, Fakultetsgatan 1, S-70281 Örebro, Sweden..
    Memedi, Mevludin
    Örebro Univ, Ctr Empir Res Informat Syst, Sch Business, Fakultetsgatan 1, S-70281 Örebro, Sweden..
    Toward Improved Treatment and Empowerment of Individuals With Parkinson Disease: Design and Evaluation of an Internet of Things System2022In: JMIR Formative Research, E-ISSN 2561-326X, Vol. 6, no 6, article id e31485Article in journal (Refereed)
    Abstract [en]

    Background: Parkinson disease (PD) is a chronic degenerative disorder that causes progressive neurological deterioration with profound effects on the affected individual's quality of life. Therefore, there is an urgent need to improve patient empowerment and clinical decision support in PD care. Home-based disease monitoring is an emerging information technology with the potential to transform the care of patients with chronic illnesses. Its acceptance and role in PD care need to be elucidated both among patients and caregivers.

    Objective: Our main objective was to develop a novel home-based monitoring system (named EMPARK) with patient and clinician interface to improve patient empowerment and clinical care in PD.

    Methods: We used elements of design science research and user-centered design for requirement elicitation and subsequent information and communications technology (ICT) development. Functionalities of the interfaces were the subject of user-centric multistep evaluation complemented by semantic analysis of the recorded end-user reactions. The ICT structure of EMPARK was evaluated using the ICT for patient empowerment model.

    Results: Software and hardware system architecture for the collection and calculation of relevant parameters of disease management via home monitoring were established. Here, we describe the patient interface and the functional characteristics and evaluation of a novel clinician interface. In accordance with our previous findings with regard to the patient interface, our current results indicate an overall high utility and user acceptance of the clinician interface. Special characteristics of EMPARK in key areas of interest emerged from end-user evaluations, with clear potential for future system development and deployment in daily clinical practice. Evaluation through the principles of ICT for patient empowerment model, along with prior findings from patient interface evaluation, suggests that EMPARK has the potential to empower patients with PD.

    Conclusions: The EMPARK system is a novel home monitoring system for providing patients with PD and the care team with feedback on longitudinal disease activities. User-centric development and evaluation of the system indicated high user acceptance and usability. The EMPARK infrastructure would empower patients and could be used for future applications in daily care and research.

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  • 39. Khan, Taha
    et al.
    Grenholm, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Computer Vision Methods for Parkinsonian Gait Analysis: A Review onPatents2013In: Recent Patents on Biomedical Engineering, ISSN 1874-7647, Vol. 6, p. 97-108Article in journal (Refereed)
  • 40.
    Khan, Taha
    et al.
    Dalarna Univ, Sch Technol & Business Studies, S-79188 Falun, Sweden; Malardalen Univ, Sch Innovat Design & Technol, S-72123 Vasteras, Sweden.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Westin, Jerker
    Dalarna Univ, Sch Technol & Business Studies, S-79188 Falun, Sweden.
    Dougherty, Mark
    Dalarna Univ, Sch Technol & Business Studies, S-79188 Falun, Sweden.
    A computer vision framework for finger-tapping evaluation in Parkinson's disease2014In: Artificial Intelligence in Medicine, ISSN 0933-3657, E-ISSN 1873-2860, Vol. 60, no 1, p. 27-40Article in journal (Refereed)
    Abstract [en]

    Objectives: The rapid finger-tapping test (RFT) is an important method for clinical evaluation of movement disorders, including Parkinson's disease (PD). In clinical practice, the naked-eye evaluation of RFT results in a coarse judgment of symptom scores. We introduce a novel computer-vision (CV) method for quantification of tapping symptoms through motion analysis of index-fingers. The method is unique as it utilizes facial features to calibrate tapping amplitude for normalization of distance variation between the camera and subject. Methods: The study involved 387 video footages of RFT recorded from 13 patients diagnosed with advanced PD. Tapping performance in these videos was rated by two clinicians between the symptom severity levels ('0: normal' to '3: severe') using the unified Parkinson's disease rating scale motor examination of finger-tapping (UPDRS-FT). Another set of recordings in this study consisted of 84 videos of RFT recorded from 6 healthy controls. These videos were processed by a CV algorithm that tracks the index-finger motion between the video-frames to produce a tapping time-series. Different features were computed from this time series to estimate speed, amplitude, rhythm and fatigue in tapping. The features were trained in a support vector machine (1) to categorize the patient group between UPDRS-FT symptom severity levels, and (2) to discriminate between PD patients and healthy controls. Results: A new representative feature of tapping rhythm, 'cross-correlation between the normalized peaks' showed strong Guttman correlation (mu(2) = -0.80) with the clinical ratings. The classification of tapping features using the support vector machine classifier and 10-fold cross validation categorized the patient samples between UPDRS-FT levels with an accuracy of 88%. The same classification scheme discriminated between RFT samples of healthy controls and PD patients with an accuracy of 95%. Conclusion: The work supports the feasibility of the approach, which is presumed suitable for PD monitoring in the home environment. The system offers advantages over other technologies (e.g. magnetic sensors, accelerometers, etc.) previously developed for objective assessment of tapping symptoms.

  • 41. Kristiansen, Ivar
    et al.
    Bingefors, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Isacson, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Short-Term Cost and Health Consequences of Duodenal Levodopa Infusion in Advanced Parkinson's Disease in Sweden: An Exploratory Study2009In: Applied Health Economics and Health Policy, ISSN 1175-5652, E-ISSN 1179-1896, Vol. 7, no 3, p. 167-180Article in journal (Refereed)
    Abstract [en]

    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.

  • 42.
    Kumlien, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Akutneurologi2012In: Neurologi / [ed] Fagius J, Nyholm D, Liber, 2012Chapter in book (Other (popular science, discussion, etc.))
  • 43. LeWitt, Peter
    et al.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    New developments in levodopa therapy2004In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 62, no Suppl. 1, p. s9-S16Article in journal (Refereed)
    Abstract [en]

    More than 30 years after its development, levodopa is still the most effective treatment for the symptomatic control of Parkinson's disease (PD). Although a number of therapies have been developed in an attempt to improve PD management, such as dopaminergic agonists and inhibitors of COMT and MAO-B, most patients still depend on levodopa alone because of its superior ability to control PD symptoms. The issue of toxicity has been raised by in vitro studies suggesting that levodopa might be toxic to dopaminergic neurons, but this has since been answered by in vivo studies finding no evidence of toxicity and possibly even neurotrophic-like effects. A more pressing concern regarding levodopa is its association with the development of motor complications after long-term use. Pulsatile dopaminergic stimulation as a result of erratic absorption and the short half-life of levodopa have been central issues in attempts to explain this occurrence. Evidence suggests that altering the delivery of levodopa to provide a more continuous supply of this drug to the brain may result in improved control of PD symptoms.

  • 44.
    Lubberink, Mark
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Widström, Charles
    Uppsala Univ Hosp, Uppsala, Sweden.
    Jonasson, My
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Uppsala, Sweden.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fällmar, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Uppsala, Sweden.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Uppsala Univ Hosp, Uppsala, Sweden.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Uppsala, Sweden.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Uppsala, Sweden.
    Differential diagnosis of patients with parkinsonian syndrome using multilinear regression to disease-specific C-11-PE2I-PET templates and classification tree learning2018In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, p. S409-S409Article in journal (Other academic)
  • 45. Lundin, Anders
    et al.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Funktionella neurologiska sjukdomar2020In: Neurologi / [ed] Nyholm, Burman, Liber, 2020Chapter in book (Other academic)
  • 46. Marrinan, Sarah L
    et al.
    Otiker, Tal
    Vasist, Lakshmi S
    Gibson, Rachel A
    Sarai, Bhopinder K
    Barton, Matthew E
    Richards, Duncan B
    Hellström, Per M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Dukes, George E
    Burn, David J
    A randomized, double-blind, placebo-controlled trial of camicinal in Parkinson's disease.2018In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 33, no 2, p. 329-332Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Delayed gastric emptying may impair l-dopa absorption, contributing to motor fluctuations. We evaluated the effect of camicinal (GSK962040), a gastroprokinetic, on the absorption of l-dopa and symptoms of PD.

    METHODS: Phase II, double-blind, placebo-controlled trial. Participants were randomized to receive camicinal 50 mg once-daily (n = 38) or placebo (n = 20) for 7 to 9 days.

    RESULTS: l-dopa exposure was similar with coadministration of camicinal compared to placebo. Median time to maximum l-dopa concentration was reduced, indicating more rapid absorption of l-dopa. Camicinal resulted in significant reduction in OFF time (-2.31 hours; 95% confidence interval: -3.71, -0.90), significant increase in ON time (+1.88 hours; 95% confidence interval: 0.28, 3.48) per day, and significant decrease in mean total MDS-UPDRS score (-12.5; 95% confidence interval: -19.67, -5.29). Camicinal treatment was generally well tolerated.

    CONCLUSIONS: PD symptom improvement with camicinal occurred in parallel with more rapid absorption of l-dopa. This study provides evidence of an improvement of the motor response to l-dopa in people with PD treated with camicinal 50 mg once-daily compared with placebo, which will require further evaluation.

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  • 47.
    Matic, Teodora
    et al.
    Univ Ljubljana, Fac Comp & Informat Sci, Ljubljana, Slovenia.
    Aghanavesi, Somayeh
    Dalarna Univ, Sch Technol & Business Studies, Comp Engn, Dalarna, Sweden.
    Memedi, Mevludin
    Orebro Univ, Business Sch, Informat, Orebro, Sweden.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Bergquist, Filip
    Univ Gothenburg, Dept Pharmacol, Gothenburg, Sweden.
    Groznik, Vida
    Univ Ljubljana, Fac Comp & Informat Sci, Ljubljana, Slovenia;Univ Primorska, Fac Math Nat Sci & Informat Technol, Koper, Slovenia.
    Zabkar, Jure
    Univ Ljubljana, Fac Comp & Informat Sci, Ljubljana, Slovenia.
    Sadikov, Aleksander
    Univ Ljubljana, Fac Comp & Informat Sci, Ljubljana, Slovenia.
    Unsupervised Learning from Motion Sensor Data to Assess the Condition of Patients with Parkinson's Disease2019In: ARTIFICIAL INTELLIGENCE IN MEDICINE, AIME 2019 / [ed] Riano, D Wilk, S TenTeije, A, 2019, p. 420-424Conference paper (Refereed)
    Abstract [en]

    Parkinson's disease (PD) is a chronic neurodegenerative disorder that predominantly affects the patient's motor system, resulting in muscle rigidity, bradykinesia, tremor, and postural instability. As the disease slowly progresses, the symptoms worsen, and regular monitoring is required to adjust the treatment accordingly. The objective evaluation of the patient's condition is sometimes rather difficult and automated systems based on various sensors could be helpful to the physicians. The data in this paper come from a clinical study of 19 advanced PD patients with motor fluctuations. The measurements used come from the motion sensors the patients wore during the study. The paper presents an unsupervised learning approach applied on this data with the aim of checking whether sensor data alone can indicate the patient's motor state. The rationale for the unsupervised approach is that there was significant inter-physician disagreement on the patient's condition (target value for supervised machine learning). The input to clustering came from sensor data alone. The resulting clusters were matched against the physicians' estimates showing relatively good agreement.

  • 48. Memedi, Mevludin
    et al.
    Khan, Taha
    Grenholm, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Westin, Jerker
    Automatic and Objective Assessment of Alternating Tapping Performance in Parkinson's Disease2013In: Sensors, E-ISSN 1424-8220, Vol. 13, no 12, p. 16965-16984Article in journal (Refereed)
    Abstract [en]

    This paper presents the development and evaluation of a method for enabling quantitative and automatic scoring of alternating tapping performance of patients with Parkinson’s disease (PD). Ten healthy elderly subjects and 95 patients in different clinical stages of PD have utilized a touch-pad handheld computer to perform alternate tapping tests in their home environments. First, a neurologist used a web-based system to visually assess impairments in four tapping dimensions (‘speed’, ‘accuracy’, ‘fatigue’ and ‘arrhythmia’) and a global tapping severity (GTS). Second, tapping signals were processed with time series analysis and statistical methods to derive 24 quantitative parameters. Third, principal component analysis was used to reduce the dimensions of these parameters and to obtain scores for the four dimensions. Finally, a logistic regression classifier was trained using a 10-fold stratified cross-validation to map the reduced parameters to the corresponding visually assessed GTS scores. Results showed that the computed scores correlated well to visually assessed scores and were significantly different across Unified Parkinson’s Disease Rating Scale scores of upper limb motor performance. In addition, they had good internal consistency, had good ability to discriminate between healthy elderly and patients in different disease stages, had good sensitivity to treatment interventions and could reflect the natural disease progression over time. In conclusion, the automatic method can be useful to objectively assess the tapping performance of PD patients and can be included in telemedicine tools for remote monitoring of tapping.

  • 49.
    Memedi, Mevludin
    et al.
    Dalarna Univ, Sch Technol & Business Studies, Comp Engn, S-79188 Falun, Sweden..
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Johansson, Anders
    Karolinska Inst, Dept Clin Neurosci, Neurol, S-14186 Huddinge, Sweden..
    Palhagen, Sven
    Karolinska Univ Hosp, Dept Neurol, S-17177 Stockholm, Sweden..
    Willows, Thomas
    Karolinska Univ Hosp, Dept Neurol, S-17177 Stockholm, Sweden..
    Widner, Hakan
    Skane Univ Hosp, Dept Neurol, S-22185 Lund, Sweden..
    Linder, Jan
    Umea Univ, Dept Pharmacol & Clin Neurosci, S-90187 Umea, Sweden..
    Westin, Jerker
    Dalarna Univ, Sch Technol & Business Studies, Comp Engn, S-79188 Falun, Sweden..
    Validity and Responsiveness of At-Home Touch Screen Assessments in Advanced Parkinson's Disease2015In: IEEE journal of biomedical and health informatics, ISSN 2168-2194, E-ISSN 2168-2208, Vol. 19, no 6, p. 1829-1834Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate if a telemetry test battery can be used to measure effects of Parkinson's disease (PD) treatment intervention and disease progression in patients with fluctuations. Sixty-five patients diagnosed with advanced PD were recruited in an open longitudinal 36-month study; 35 treated with levodopa-carbidopa intestinal gel (LCIG) and 30 were candidates for switching from oral PD treatment to LCIG. They utilized a test battery, consisting of self-assessments of symptoms and fine motor tests (tapping and spiral drawings), four times per day in their homes during week-long test periods. The repeated measurements were summarized into an overall test score (OTS) to represent the global condition of the patient during a test period. Clinical assessments included ratings on unified PD rating scale (UPDRS) and 39-item PD questionnaire (PDQ-39) scales. In LCIG-naive patients, the mean OTS compared to baseline was significantly improved from the first test period on LCIG treatment until month 24. In LCIG-non naive patients, there were no significant changes in the mean OTS until month 36. The OTS correlated adequately with total UPDRS (rho = 0.59) and total PDQ-39 (0.59). Responsiveness measured as effect size was 0.696 and 0.536 for OTS and UPDRS, respectively. The trends of the test scores were similar to the trends of clinical rating scores but the dropout rate was high. Correlations betweenOTS and clinical rating scales were adequate indicating that the test battery contains important elements of the information of well-established scales. The responsiveness and reproducibility were better for OTS than for total UPDRS.

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  • 50. Memedi, Mevludin
    et al.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Westin, Jerker
    Combined fine-motor tests and self-assessments for remote detection of motor fluctuations2013In: Recent Patents on Biomedical Engineering, ISSN 1874-7647, Vol. 6, no 2, p. 127-135Article in journal (Refereed)
    Abstract [en]

    A major problem with the clinical management of fluctuating movement disorders, e.g. Parkinson’s disease (PD), is the large variability in manifestation of symptoms among patients. In this condition, frequent measurements which account for both patient-reported and objective assessments are needed in order to capture symptom fluctuations, with the purpose to optimize therapy. The main focus of this paper is to present a mobile-based system for enabling remote monitoring of PD patients from their home environment conditions. The system consists of a patient diary section for collecting patient-based self-assessments, a motor test section for collecting fine motor movements through upper limb motor tests, and a scheduler for restricting operation to a multitude of predetermined limited time intervals. The system processes and compiles time series data into different summary scores representing symptom severity. In addition, the paper presents a review of recent inventions which were filed after year 2000 in the field of telemedicine applications. The review includes a summary of systems and methods which enable remote symptom assessments of patients, not necessarily suffering from movement disorders, through repeated measurements and which take into account their subjective and/or objective health indicators. The findings conclude that there are a small number of inventions which collect subjective and objective health measures in telemedicine settings. Consequently, there is a lack of mechanisms that combine these two types of information into scores to provide a more in-depth assessment of the patient’s general health, their motor and non-motor symptom fluctuations and treatment effects. The paper also provides a discussion concerning different approaches for analyzing and combining subjective and objective measures, and handling data from longitudinal studies.

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