| Zugriffsnummer | 43449 |
| Dokumenttyp | Zeitschriftenartikel |
| Peer Review | mit Peer Review |
| Sprache | Englisch |
| Titel | Brain iron and metabolic abnormalities in C19orf12 mutation carriers: A 7.0 tesla MRI study in mitochondrial membrane protein- associated neurodegeneration. |
| Autor(in); Institution |
Dusek, P.; Department of Neurology and Centre of Clinical Neuroscience, Charles University, 1st Faculty of Medicine and General University Hospital in Prague, Prague, CZECH REPUBLIC
Mekle, Ralf; 8.1, Biomedizinische Magnetresonanz, PTB-Berlin
Skowronska, M.; 2nd Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, POLAND
Acosta-Cabronero, J.; Wellcome Centre for Human Neuroimaging, UCL Institute of Neurology, University College London, London, UK
Huelnhagen, T.; Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, GERMANY
Robinson, S.D.; High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, AUSTRIA
Schubert, Frank; 8.1, Biomedizinische Magnetresonanz, PTB-Berlin
Deschauer, M.; Department of Neurology, Technical University Munich, Munich, GERMANY
Els, ; Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, GERMANY
Ittermann, Bernd; 8.1, Biomedizinische Magnetresonanz, PTB-Berlin
Schottmann, G.; NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité-Universitaetsmedizin Berlin, Berlin, GERMANY
Madai, V.; Center for Stroke Research Berlin (CSB), Charité Universitätsmedizin Berlin, Berlin, GERMANY; Department of Neurosurgery, Charité Universitätsmedizin Berlin, Berlin, GERMANY
Paul, F.; NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité-Universitaetsmedizin Berlin, Berlin, GERMANY
Klopstock, T.; Department of Neurology with Friedrich-Baur-Institute, Ludwig-Maximilians-University of Munich, Munich, GERMANY; German Center for Neurodegenerative Diseases (DZNE), Munich, GERMANY; Munich Cluster for Systems Neurology (SyNergy), Munich, GERMANY
Kmiec, T.; Department of Neurology and Epileptology, The Children's Memorial Health Institute, Warsaw, POLAND
Niendorf, T.; Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, GERMANY
Wuerfel, J.; NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité-Universitaetsmedizin Berlin, Berlin, GERMANY; Medical Image Analysis Center and Department Biomedical Engineering, University Basel, Basel, SWITZERLAND
Schneider, S.A.; Neurology Department, Ludwig Maximilians-University of Munich, GERMANY
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| Quelle/Jahr | Movement Disorders: 35 (2020), 1, 142 - 150 |
| ISSN | 0885-3185 (PRINT) ; 1531-8257 (ONLINE) |
| DOI | |
| Verlag | Hoboken, NJ: Wiley-Blackwell |
| Freie Schlagworte | 7 Tesla MRI ; glutamate; magnetic resonance spectroscopy ; mitochondrial membrane protein-associated neurodegeneration (MPAN) ; neurodegeneration with brain iron accumulation (NBIA) ; quantitative susceptibility mapping ; iron |
| Zusammenfassung | BACKGROUND: Mitochondrial membrane protein-associated neurodegeneration is an autosomal-recessive disorder caused by C19orf12 mutations and characterized by iron deposits in the basal ganglia. OBJECTIVES: The aim of this study was to quantify iron concentrations in deep gray matter structures using quantitative susceptibility mapping MRI and to characterize metabolic abnormalities in the pyramidal pathway using 1 H MR spectroscopy in clinically manifesting membrane protein-associated neurodegeneration patients and asymptomatic C19orf12 gene mutation heterozygous carriers. METHODS: We present data of 4 clinically affected membrane protein-associated neurodegeneration patients (mean age: 21.0 ± 2.9 years) and 9 heterozygous gene mutation carriers (mean age: 50.4 ± 9.8 years), compared to age-matched healthy controls. MRI assessments were performed on a 7.0 Tesla whole-body system, consisting of whole-brain gradient-echo scans and short echo time, single- volume MR spectroscopy in the white matter of the precentral/postcentral gyrus. Quantitative susceptibility mapping, a surrogate marker for iron concentration, was performed using a state-of-the-art multiscale dipole inversion approach with focus on the globus pallidus, thalamus, putamen, caudate nucleus, and SN. RESULTS AND CONCLUSION: In membrane protein-associated neurodegeneration patients, magnetic susceptibilities were 2 to 3 times higher in the globus pallidus (P = 0.02) and SN (P = 0.02) compared to controls. In addition, significantly higher magnetic susceptibility was observed in the caudate nucleus (P = 0.02). Non-manifesting heterozygous mutation carriers exhibited significantly increased magnetic susceptibility (relative to controls) in the putamen (P = 0.003) and caudate nucleus (P = 0.001), which may be an endophenotypic marker of genetic heterozygosity. MR spectroscopy revealed significantly increased levels of glutamate, taurine, and the combined concentration of glutamate and glutamine in membrane protein-associated neurodegeneration, which may be a correlate of corticospinal pathway dysfunction frequently observed in membrane protein-associated neurodegeneration patients. |
| Themenbereich der Metrologie | Metrologie in der Medizin |
| Forschungsprojekt | Else Kröner-Fresenius-Stiftung, the Eva Luise und Horst Köhler Stiftung, the German Federal Ministry of Education and Research and by the Czech Ministry of Health, grant no. 15-25602A. |
Zitierung
Dusek, P., Mekle, R., Skowronska, M., Acosta-Cabronero, J., Huelnhagen, T., Robinson, S., Schubert, F., Deschauer, M., Els, Ittermann, B., Schottmann, G., Madai, V., Paul, F., Klopstock, T., Kmiec, T., Niendorf, T., Wuerfel, J., & Schneider, S. (2020). Brain iron and metabolic abnormalities in C19orf12 mutation carriers: A 7.0 tesla MRI study in mitochondrial membrane protein- associated neurodegeneration. Movement Disorders, 35(1), 142–150. https://doi.org/10.1002/mds.27827