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11. Decision Support System for the Diagnosis of Parkinson’s Disease

Author

Ericsson, Anders, Lonsdale, Markus Nowak, Astrom, Kalle, Edenbrandt, Lars, Friberg, Lars, Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Dough, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Kalviainen, Heikki, editor, Parkkinen, Jussi, editor, and Kaarna, Arto, editor

Published
2005
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14. 18

Author

Marner, Lisbeth, Korsholm, Kirsten, Anderberg, Lasse, Lonsdale, Markus N., Jensen, Mads Radmer, Brødsgaard, Eva, Denholt, Charlotte L., Gillings, Nic, Law, Ian, Friberg, Lars, Marner, Lisbeth, Korsholm, Kirsten, Anderberg, Lasse, Lonsdale, Markus N., Jensen, Mads Radmer, Brødsgaard, Eva, Denholt, Charlotte L., Gillings, Nic, Law, Ian, and Friberg, Lars

Abstract

Background: Dopamine transporter (DAT) imaging of striatum is clinically used in Parkinson’s disease (PD) and neurodegenerative parkinsonian syndromes (PS) especially in the early disease stages. The aim of the present study was to evaluate the diagnostic performance of the recently developed tracer for DAT imaging [18F]FE-PE2I PET/CT to the reference standard [123I]FP-CIT SPECT. Methods: Ninety-eight unselected patients referred for DAT imaging were included prospectively and consecutively and evaluated with [18F]FE-PE2I PET/CT and [123I]FP-CIT SPECT on two separate days. PET and SPECT scans were categorized independently by two blinded expert readers as either normal, vascular changes, or mixed. Semiquantitative values were obtained for each modality and compared regarding effect size using Glass’ delta. Results: Fifty-six of the [123I]FP-CIT SPECT scans were considered abnormal (52 caused by PS, 4 by infarctions). Using [18F]FE-PE2I PET/CT, 95 of the 98 patients were categorized identically to SPECT as PS or non-PS with a sensitivity of 0.94 [0.84–0.99] and a specificity of 1.00 [0.92–1.00]. Inter-reader agreement for [18F]FE-PE2I PET with a kappa of 0.97 [0.89–1.00] was comparable to the agreement for [123I]FP-CIT SPECT of 0.96 [0.76–1.00]. Semiquantitative values for short 10-min reconstructions of [18F]FE-PE2I PET/CT were comparable to longer reconstructions. The effect size for putamen/caudate nucleus ratio was significantly increased using PET compared to SPECT. Conclusions: The high correspondence of [18F]FE-PE2I PET compared to reference standard [123I]FP-CIT SPECT establishes [18F]FE-PE2I PET as a feasible PET tracer for clinical use with favourable scan logistics.

Published
2022

17. Missense dopamine transporter mutations associate with adult parkinsonism and ADHD

Author

Hansen, Freja H., Skjorringe, Tina, Yasmeen, Saiqa, Arends, Natascha V., Sahai, Michelle A., Erreger, Kevin, Andreassen, Thorvald F., Holy, Marion, Hamilton, Peter J., Neergheen, Viruna, Karlsborg, Merete, Newman, Amy H., Pope, Simon, Heales, Simon J.R., Friberg, Lars, Law, Ian, Pinborg, Lars H., Sitte, Harald H., Loland, Claus, Shi, Lei, Weinstein, Harel, Galli, Aurelio, Hjermind, Lena E., Moller, Lisbeth B., and Gether, Ulrik

Subjects
Genetic variation -- Identification and classification, Membrane proteins -- Genetic aspects, Parkinson's disease -- Genetic aspects -- Development and progression, Attention-deficit hyperactivity disorder -- Genetic aspects -- Development and progression, Health care industry
Abstract

Parkinsonism and attention deficit hyperactivity disorder (ADHD) are widespread brain disorders that involve disturbances of dopaminergic signaling. The sodium-coupled dopamine transporter (DAT) controls dopamine homeostasis, but its contribution to disease remains poorly understood. Here, we analyzed a cohort of patients with atypical movement disorder and identified 2 DAT coding variants, DAT-Ile312Phe and a presumed de novo mutant DAT-Asp421Asn, in an adult male with early-onset parkinsonism and ADHD. According to DAT single-photon emission computed tomography (DAT-SPECT) scans and a fluoro-deoxy-glucose-PET/MRI (FDG-PET/MRI) scan, the patient suffered from progressive dopaminergic neurodegeneration. In heterologous cells, both DAT variants exhibited markedly reduced dopamine uptake capacity but preserved membrane targeting, consistent with impaired catalytic activity. Computational simulations and uptake experiments suggested that the disrupted function of the DAT- Asp421Asn mutant is the result of compromised sodium binding, in agreement with Asp421 coordinating sodium at the second sodium site. For DAT-Asp421Asn, substrate efflux experiments revealed a constitutive, anomalous efflux of dopamine, and electrophysiological analyses identified a large cation leak that might further perturb dopaminergic neurotransmission. Our results link specific DAT missense mutations to neurodegenerative early-onset parkinsonism. Moreover, the neuropsychiatric comorbidity provides additional support for the idea that DAT missense mutations are an ADHD risk factor and suggests that complex DAT genotype and phenotype correlations contribute to different dopaminergic pathologies., Introduction Dopamine is an important neurotransmitter regulating motor activity, cognition, neuroendocrine functions, and reward mechanisms. Moreover, disturbances in dopaminergic signaling are of central importance in several common brain diseases including [...]

Published
2014
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27. [18F]FE-PE2I PET is a feasible alternative to [123I]FP-CIT SPECT for dopamine transporter imaging in clinically uncertain parkinsonism.

Author

Marner, Lisbeth, Korsholm, Kirsten, Anderberg, Lasse, Lonsdale, Markus N., Jensen, Mads Radmer, Brødsgaard, Eva, Denholt, Charlotte L., Gillings, Nic, Law, Ian, and Friberg, Lars

Subjects
POSITRON emission tomography, PARKINSON'S disease, CAUDATE nucleus, PARKINSONIAN disorders, DOPAMINE, SINGLE-photon emission computed tomography, CARDIAC radionuclide imaging
Abstract

Background: Dopamine transporter (DAT) imaging of striatum is clinically used in Parkinson's disease (PD) and neurodegenerative parkinsonian syndromes (PS) especially in the early disease stages. The aim of the present study was to evaluate the diagnostic performance of the recently developed tracer for DAT imaging [18F]FE-PE2I PET/CT to the reference standard [123I]FP-CIT SPECT. Methods: Ninety-eight unselected patients referred for DAT imaging were included prospectively and consecutively and evaluated with [18F]FE-PE2I PET/CT and [123I]FP-CIT SPECT on two separate days. PET and SPECT scans were categorized independently by two blinded expert readers as either normal, vascular changes, or mixed. Semiquantitative values were obtained for each modality and compared regarding effect size using Glass' delta. Results: Fifty-six of the [123I]FP-CIT SPECT scans were considered abnormal (52 caused by PS, 4 by infarctions). Using [18F]FE-PE2I PET/CT, 95 of the 98 patients were categorized identically to SPECT as PS or non-PS with a sensitivity of 0.94 [0.84–0.99] and a specificity of 1.00 [0.92–1.00]. Inter-reader agreement for [18F]FE-PE2I PET with a kappa of 0.97 [0.89–1.00] was comparable to the agreement for [123I]FP-CIT SPECT of 0.96 [0.76–1.00]. Semiquantitative values for short 10-min reconstructions of [18F]FE-PE2I PET/CT were comparable to longer reconstructions. The effect size for putamen/caudate nucleus ratio was significantly increased using PET compared to SPECT. Conclusions: The high correspondence of [18F]FE-PE2I PET compared to reference standard [123I]FP-CIT SPECT establishes [18F]FE-PE2I PET as a feasible PET tracer for clinical use with favourable scan logistics. [ABSTRACT FROM AUTHOR]

Published
2022
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29. Hemodynamic and neuroendocrine responses to changes in sodium intake in compensated heart failure

Author

Damgaard, Morten, Norsk, Peter, Gustafsson, Finn, Kanters, Jorgen K., Christensen, Niels Juel, Bie, Peter, Friberg, Lars, and Gadsboll, Niels

Subjects
Exercise -- Health aspects, Exercise -- Research, Heart failure -- Research, Sodium in the body -- Health aspects, Sodium in the body -- Research, Biological sciences
Abstract

Patients with untreated heart failure (HF) exhibit a blunted hemodynamic and neuroendocrine response to a high sodium intake, leading to excessive sodium and water retention. However, it is not known whether this is the case for patients with compensated HF receiving angiotensin-converting enzyme inhibitors and [beta]-adrenoreceptor blockers. Therefore, we determined the hemodynamic and neuroendocrine responses to 1 wk of a low-sodium diet (70 mmol/day) and 1 wk of a high-sodium diet (250 mmol/day) in 12 HF patients and 12 age-matched controls in a randomized, balanced fashion. During steady-state conditions, hemodynamic and neuroendocrine examinations were performed at rest and during bicycle exercise. In seated HF patients, high sodium intake increased body weight (1.6 [+ or -] 0.4%), plasma volume (9 [+ or -] 2%), cardiac index (14 [+ or -] 6%), and stroke volume index (21 [+ or -] 5%), whereas mean arterial pressure was unchanged. Therefore, the total peripheral resistance decreased by 10 [+ or -] 4%. Similar hemodynamic changes were observed during an incremental bicycle exercise test. Plasma concentrations of angiotensin II and norepinephrine were suppressed, whereas plasma pro-B-type natriuretic peptide remained unchanged. In conclusion, high sodium intake was tolerated without any excessive sodium and water retention in medically treated patients with compensated HF. The observation that high sodium intake improves cardiac performance, induces peripheral vasodilatation, and suppresses the release of vasoconstrictor hormones does not support the advice for HF patients to restrict dietary sodium. dietary sodium; plasma volume; exercise

Published
2006

42. Cadmium

Author

NORDBERG, GUNNAR F., primary, NOGAWA, KOJI, additional, NORDBERG, MONICA, additional, and FRIBERG, LARS T., additional

Published
2007
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45. Nursing Programme

Author

Beanland, S., Sproat, L. J., Darowski, M. J., Norman, Surgery S., Thompson, L., Medicus, L., Huwiler, Eliane, Kobel, Eva, Leijonmarck, A., Lundeberg, S., Ferngren, H., Lindholm, A. C., Olsson, G. L., Duvndam, Anita, v. d. Sluis, Sonia, Craig J., Darbyshire A., Horrox F., Kitchiner D., Chapman S., Herouvin L., Courtney J., Mok Q., Danschutter D., Goris J., Ramet J., Franco A., Skogby, Maria, Mellgren, Karin, Friberg, Lars-Göran, Mellgren, Gösta, Wadenvik, Hans, Hermana Tezanos M. T., Pilar Orive J., Latorre Garcia J., Lizarraga Azparr M. A., Lopez Bayón J., Jakomin, M., Kranjec, T., Sajovic, V., Kodran, E., Primožič, J., Wierema, Joan, Mourik, Marjan, Mourik M., Smits, Corina, Molenaar J. C., Tibboel D., de Boer, Josien, Bouwmeester J., Sonius, E. M., Verhoeven, J. J., Joosten, K. F. M., vd. Vooft, E., Petreska, M., Moder, B., Janičijevič, Z., Kovač, A., Warren, Muir, Maryse, Blondel, Rhonda, Foltz, Martine, Farine, Isabelle, Grillet, Christa, Bosson, Andrea, Goelz, Pascale, Helmer, Mikaelian, P., Ronin, E., Claris, O., Salle, B. L., Schindler, Monika, Braganti, I., Despianques, I., Cimeno, R., Métivier, M. T., Papez, I., Delaitre, C., Schlumberger, E., Jeanne, C., Minier, D., Egrot, F., Saidani, S., and REA PED working group

Published
1996
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