Search

Your search keyword '"Kamm, Christoph"' showing total 225 results
Start Over Author "Kamm, Christoph"
225 results on '"Kamm, Christoph"'

1. 5qSMA: standardised retrospective natural history assessment in 268 patients with four copies of SMN2

Author

Vill, Katharina, Tacke, Moritz, König, Anna, Baumann, Matthias, Baumgartner, Manuela, Steinbach, Meike, Bernert, Guenther, Blaschek, Astrid, Deschauer, Marcus, Flotats-Bastardas, Marina, Friese, Johannes, Goldbach, Susanne, Gross, Martin, Günther, René, Hahn, Andreas, Hagenacker, Tim, Hauser, Erwin, Horber, Veronka, Illsinger, Sabine, Johannsen, Jessika, Kamm, Christoph, Koch, Jan C., Koelbel, Heike, Koehler, Cornelia, Kolzter, Kirsten, Lochmüller, Hanns, Ludolph, Albert, Mensch, Alexander, Meyer zu Hoerste, Gerd, Mueller, Monika, Mueller-Felber, Wolfgang, Neuwirth, Christoph, Petri, Susanne, Probst-Schendzielorz, Kristina, Pühringer, Manuel, Steinbach, Robert, Schara-Schmidt, Ulrike, Schimmel, Mareike, Schrank, Bertold, Schwartz, Oliver, Schlachter, Kurt, Schwerin-Nagel, Annette, Schreiber, Gudrun, Smitka, Martin, Topakian, Raffi, Trollmann, Regina, Tuerk, Matthias, Theophil, Manuela, Rauscher, Christian, Vorgerd, Mathias, Walter, Maggie C., Weiler, Markus, Weiss, Claudia, Wilichowski, Ekkehard, Wurster, Claudia D., Wunderlich, Gilbert, Zeller, Daniel, Ziegler, Andreas, Kirschner, Janbernd, and Pechmann, Astrid

Published
2024
Full Text
View/download PDF

2. Long-term efficacy and safety of nusinersen in adults with 5q spinal muscular atrophy: a prospective European multinational observational study

Author

Günther, René, Wurster, Claudia Diana, Brakemeier, Svenja, Osmanovic, Alma, Schreiber-Katz, Olivia, Petri, Susanne, Uzelac, Zeljko, Hiebeler, Miriam, Thiele, Simone, Walter, Maggie C., Weiler, Markus, Kessler, Tobias, Freigang, Maren, Lapp, Hanna Sophie, Cordts, Isabell, Lingor, Paul, Deschauer, Marcus, Hahn, Andreas, Martakis, Kyriakos, Steinbach, Robert, Ilse, Benjamin, Rödiger, Annekathrin, Bellut, Julia, Nentwich, Julia, Zeller, Daniel, Muhandes, Mohamad Tareq, Baum, Tobias, Christoph Koch, Jan, Schrank, Bertold, Fischer, Sophie, Hermann, Andreas, Kamm, Christoph, Naegel, Steffen, Mensch, Alexander, Weber, Markus, Neuwirth, Christoph, Lehmann, Helmar C., Wunderlich, Gilbert, Stadler, Christian, Tomforde, Maike, George, Annette, Groß, Martin, Pechmann, Astrid, Kirschner, Janbernd, Türk, Matthias, Schimmel, Mareike, Bernert, Günther, Martin, Pascal, Rauscher, Christian, Meyer zu Hörste, Gerd, Baum, Petra, Löscher, Wolfgang, Flotats-Bastardas, Marina, Köhler, Cornelia, Probst-Schendzielorz, Kristina, Goldbach, Susanne, Schara-Schmidt, Ulrike, Müller-Felber, Wolfgang, Lochmüller, Hanns, von Velsen, Otgonzul, Kleinschnitz, Christoph, Ludolph, Albert C., and Hagenacker, Tim

Published
2024
Full Text
View/download PDF

3. Tremor is associated with familial clustering of dystonia

Author

Loens, Sebastian, Hamami, Feline, Lohmann, Katja, Odorfer, Thorsten, Ip, Chi Wang, Zittel, Simone, Zeuner, Kirsten E., Everding, Judith, Becktepe, Jos, Marth, Katrin, Borngräber, Friederike, Kollewe, Katja, Kamm, Christoph, Kühn, Andrea A., Gelderblom, Mathias, Volkmann, Jens, Klein, Christine, and Bäumer, Tobias

Published
2023
Full Text
View/download PDF

4. Large-Scale Screening: Phenotypic and Mutational Spectrum in Isolated and Combined Dystonia Genes

Author

Federal Ministry of Education and Research (Germany), German Research Foundation, Jesús Maestre, Silvia [0000-0002-1874-4628], Mir, Pablo [0000-0003-1656-302X], Thomsen, Mirja, Marth, Katrin, Loens, Sebastian, Everding, Judith, Junker, Johanna, Borngräber, Friederike, Ott, Fabian, Jesús Maestre, Silvia, Gelderblom, Mathias, Odorfer, Thorsten, Kuhlenbäumer, Gregor, Kim, Han-Joon, Schaeffer, Eva, Becktepe, Jos, Kasten, Meike, Brüggemann, Norbert, Pfister, Robert, Kollewe, Katja, Krauss, Joachim K., Lohmann, Ebba, Hinrichs, Frauke, Berg, Daniela, Jeon, Beomseok, Busch, Hauke, Altenmüller, Eckart, Mir, Pablo, Kamm, Christoph, Volkmann, Jens, Zittel, Simone, Ferbert, Andreas, Zeuner, Kirsten E., Rolfs, Arndt, Bauer, Peter, Kühn, Andrea A., Bäumer, Tobias, Klein, Christine, Lohmann, Katja, Federal Ministry of Education and Research (Germany), German Research Foundation, Jesús Maestre, Silvia [0000-0002-1874-4628], Mir, Pablo [0000-0003-1656-302X], Thomsen, Mirja, Marth, Katrin, Loens, Sebastian, Everding, Judith, Junker, Johanna, Borngräber, Friederike, Ott, Fabian, Jesús Maestre, Silvia, Gelderblom, Mathias, Odorfer, Thorsten, Kuhlenbäumer, Gregor, Kim, Han-Joon, Schaeffer, Eva, Becktepe, Jos, Kasten, Meike, Brüggemann, Norbert, Pfister, Robert, Kollewe, Katja, Krauss, Joachim K., Lohmann, Ebba, Hinrichs, Frauke, Berg, Daniela, Jeon, Beomseok, Busch, Hauke, Altenmüller, Eckart, Mir, Pablo, Kamm, Christoph, Volkmann, Jens, Zittel, Simone, Ferbert, Andreas, Zeuner, Kirsten E., Rolfs, Arndt, Bauer, Peter, Kühn, Andrea A., Bäumer, Tobias, Klein, Christine, and Lohmann, Katja

Abstract

[Background] Pathogenic variants in several genes have been linked to genetic forms of isolated or combined dystonia. The phenotypic and genetic spectrum and the frequency of pathogenic variants in these genes have not yet been fully elucidated, neither in patients with dystonia nor with other, sometimes co-occurring movement disorders such as Parkinson's disease (PD)., [Objectives] To screen >2000 patients with dystonia or PD for rare variants in known dystonia-causing genes., [Methods] We screened 1207 dystonia patients from Germany (DysTract consortium), Spain, and South Korea, and 1036 PD patients from Germany for pathogenic variants using a next-generation sequencing gene panel. The impact on DNA methylation of KMT2B variants was evaluated by analyzing the gene's characteristic episignature., [Results] We identified 171 carriers (109 with dystonia [9.0%]; 62 with PD [6.0%]) of 131 rare variants (minor allele frequency <0.005). A total of 52 patients (48 dystonia [4.0%]; four PD [0.4%, all with GCH1 variants]) carried 33 different (likely) pathogenic variants, of which 17 were not previously reported. Pathogenic biallelic variants in PRKRA were not found. Episignature analysis of 48 KMT2B variants revealed that only two of these should be considered (likely) pathogenic., [Conclusion] This study confirms pathogenic variants in GCH1, GNAL, KMT2B, SGCE, THAP1, and TOR1A as relevant causes in dystonia and expands the mutational spectrum. Of note, likely pathogenic variants only in GCH1 were also found among PD patients. For DYT-KMT2B, the recently described episignature served as a reliable readout to determine the functional effect of newly identified variants.

Published
2024

5. Nusinersen in adults with 5q spinal muscular atrophy: a non-interventional, multicentre, observational cohort study

Author

Hagenacker, Tim, Wurster, Claudia D, Günther, René, Schreiber-Katz, Olivia, Osmanovic, Alma, Petri, Susanne, Weiler, Markus, Ziegler, Andreas, Kuttler, Josua, Koch, Jan C, Schneider, Ilka, Wunderlich, Gilbert, Schloss, Natalie, Lehmann, Helmar C, Cordts, Isabell, Deschauer, Marcus, Lingor, Paul, Kamm, Christoph, Stolte, Benjamin, Pietruck, Lena, Totzeck, Andreas, Kizina, Kathrin, Mönninghoff, Christoph, von Velsen, Otgonzul, Ose, Claudia, Reichmann, Heinz, Forsting, Michael, Pechmann, Astrid, Kirschner, Janbernd, Ludolph, Albert C, Hermann, Andreas, and Kleinschnitz, Christoph

Published
2020
Full Text
View/download PDF

8. Autosomal Recessive Cerebellar Ataxias in Europe: Frequency, Onset, and Severity in 677 Patients

Author

Traschütz, Andreas, primary, Adarmes‐Gomez, Astrid D., additional, Anheim, Mathieu, additional, Baets, Jonathan, additional, Falkenburger, Björn H., additional, Gburek‐Augustat, Janina, additional, Doss, Sarah, additional, Kamm, Christoph, additional, Klivenyi, Peter, additional, Grobe‐Einsler, Marcus, additional, Klopstock, Thomas, additional, Minnerop, Martina, additional, Münchau, Alexander, additional, Pane, Chiara, additional, Renaud, Mathilde, additional, Santorelli, Filippo M., additional, Schöls, Ludger, additional, Timmann, Dagmar, additional, Vielhaber, Stefan, additional, Haack, Tobias B., additional, van de Warrenburg, Bart P., additional, Zanni, Ginevra, additional, and Synofzik, Matthis, additional

Published
2023
Full Text
View/download PDF

9. Responsiveness of the Scale for the Assessment and Rating of Ataxia and Natural History in 884 Recessive and Early Onset Ataxia Patients

Author

Federal Ministry of Education and Research (Germany), German Research Foundation, University of Tübingen, Research Foundation - Flanders, European Commission, Ministero della Salute, Ministry of Innovation and Technology (Hungary), University of Szeged, Traschütz, Andreas, Adarmes Gómez, A. D., Anheim, Mathieu, Baets, Jonathan, Brais, Bernard, Gagnon, Cynthia, Gburek-Augustat, Janina, Doss, Sarah, Hanagasi, Hasmet, Kamm, Christoph, Klivenyi, Peter, Klockgether, Thomas, Klopstock, Thomas, Minnerop, Martina, Münchau, Alexander, Renaud, Mathilde, Santorelli, Filippo M., Schöls, Ludger, Thieme, Andreas, Vielhaber, Stefan, Warrenburg, Bart van de, Zanni, Ginevra, Hilgers, Ralf-Dieter, PREPARE Consortium, Synofzik, Matthis, Federal Ministry of Education and Research (Germany), German Research Foundation, University of Tübingen, Research Foundation - Flanders, European Commission, Ministero della Salute, Ministry of Innovation and Technology (Hungary), University of Szeged, Traschütz, Andreas, Adarmes Gómez, A. D., Anheim, Mathieu, Baets, Jonathan, Brais, Bernard, Gagnon, Cynthia, Gburek-Augustat, Janina, Doss, Sarah, Hanagasi, Hasmet, Kamm, Christoph, Klivenyi, Peter, Klockgether, Thomas, Klopstock, Thomas, Minnerop, Martina, Münchau, Alexander, Renaud, Mathilde, Santorelli, Filippo M., Schöls, Ludger, Thieme, Andreas, Vielhaber, Stefan, Warrenburg, Bart van de, Zanni, Ginevra, Hilgers, Ralf-Dieter, PREPARE Consortium, and Synofzik, Matthis

Abstract

[Objective] The Scale for the Assessment and Rating of Ataxia (SARA) is the most widely applied clinical outcome assessment (COA) for genetic ataxias, but presents metrological and regulatory challenges. To facilitate trial planning, we characterize its responsiveness (including subitem-level relations to ataxia severity and patient-focused outcomes) across a large number of ataxias, and provide first natural history data for several of them., [Methods] Subitem-level correlation and distribution-based analysis of 1,637 SARA assessments in 884 patients with autosomal recessive/early onset ataxia (370 with 2–8 longitudinal assessments) were complemented by linear mixed effects modeling to estimate progression and sample sizes., [Results] Although SARA subitem responsiveness varied between ataxia severities, gait/stance showed a robust granular linear scaling across the broadest range (SARA < 25). Responsiveness was diminished by incomplete subscale use at intermediate or upper levels, nontransitions (“static periods”), and fluctuating decreases/increases. All subitems except nose-finger showed moderate-to-strong correlations to activities of daily living, indicating that metric properties—not content validity—limit SARA responsiveness. SARA captured mild-to-moderate progression in many genotypes (eg, SYNE1-ataxia: 0.55 points/yr, ataxia with oculomotor apraxia type 2: 1.14 points/yr, POLG-ataxia: 1.56 points/yr), but no change in others (autosomal recessive spastic ataxia of Charlevoix-Saguenay, COQ8A-ataxia). Whereas sensitivity to change was optimal in mild ataxia (SARA < 10), it substantially deteriorated in advanced ataxia (SARA > 25; 2.7-fold sample size). Use of a novel rank-optimized SARA without subitems finger-chase and nose-finger reduces sample sizes by 20 to 25%., [Interpretation] This study comprehensively characterizes COA properties and annualized changes of the SARA across and within a large number of ataxias. It suggests specific approaches for optimizing its responsiveness that might facilitate regulatory qualification and trial design. ANN NEUROL 2023;94:470–485

Published
2023

10. Autosomal Recessive Cerebellar Ataxias in Europe: Frequency, Onset, and Severity in 677 Patients

Author

European Commission, Federal Ministry of Education and Research (Germany), ZonMw, Dutch Research Council, Brain Foundation (The Netherlands), Jacques and Gloria Gossweiler Foundation, Radboud University, University of Tübingen, University of Szeged, Ministry of Innovation and Technology (Hungary), Research Foundation - Flanders, Ministero della Salute, Projekt DEAL, Traschütz, Andreas, Adarmes Gómez, A. D., Anheim, Mathieu, Baets, Jonathan, Falkenburger, Björn H., Gburek-Augustat, Janina, Doss, Sarah, Kamm, Christoph, Klivenyi, Peter, Grobe-Einsler, Marcus, Klopstock, Thomas, Minnerop, Martina, Münchau, Alexander, Pane, Chiara, Renaud, Mathilde, Santorelli, Filippo M., Schöls, Ludger, Timmann, Dagmar, Vielhaber, Stefan, Haack, Tobias B., Warrenburg, Bart van de, Zanni, Ginevra, Synofzik, Matthis, European Commission, Federal Ministry of Education and Research (Germany), ZonMw, Dutch Research Council, Brain Foundation (The Netherlands), Jacques and Gloria Gossweiler Foundation, Radboud University, University of Tübingen, University of Szeged, Ministry of Innovation and Technology (Hungary), Research Foundation - Flanders, Ministero della Salute, Projekt DEAL, Traschütz, Andreas, Adarmes Gómez, A. D., Anheim, Mathieu, Baets, Jonathan, Falkenburger, Björn H., Gburek-Augustat, Janina, Doss, Sarah, Kamm, Christoph, Klivenyi, Peter, Grobe-Einsler, Marcus, Klopstock, Thomas, Minnerop, Martina, Münchau, Alexander, Pane, Chiara, Renaud, Mathilde, Santorelli, Filippo M., Schöls, Ludger, Timmann, Dagmar, Vielhaber, Stefan, Haack, Tobias B., Warrenburg, Bart van de, Zanni, Ginevra, and Synofzik, Matthis

Published
2023

11. Loss of paraplegin drives spasticity rather than ataxia in a cohort of 241 patients with SPG7

Author

Coarelli, Giulia, Schule, Rebecca, van de Warrenburg, Bart P.C., De Jonghe, Peter, Ewenczyk, Claire, Martinuzzi, Andrea, Synofzik, Matthis, Hamer, Elisa G., Baets, Jonathan, Anheim, Mathieu, Schöls, Ludger, Deconinck, Tine, Masrori, Pegah, Fontaine, Bertrand, Klockgether, Thomas, DʼAngelo, Maria Grazia, Monin, Marie-Lorraine, De Bleecker, Jan, Migeotte, Isabelle, Charles, Perrine, Bassi, Maria Teresa, Klopstock, Thomas, Mochel, Fanny, Ollagnon-Roman, Elisabeth, DʼHooghe, Marc, Kamm, Christoph, Kurzwelly, Delia, Papin, Melanie, Davoine, Claire-Sophie, Banneau, Guillaume, Tezenas du Montcel, Sophie, Seilhean, Danielle, Brice, Alexis, Duyckaerts, Charles, Stevanin, Giovanni, and Durr, Alexandra

Published
2019
Full Text
View/download PDF

12. Responsiveness of the Scale for the Assessment and Rating of Ataxia and Natural History in 884 Recessive and Early Onset Ataxia Patients.

Author

Traschütz, Andreas, Adarmes‐Gómez, Astrid D., Anheim, Mathieu, Baets, Jonathan, Brais, Bernard, Gagnon, Cynthia, Gburek‐Augustat, Janina, Doss, Sarah, Hanağası, Haşmet A., Kamm, Christoph, Klivenyi, Peter, Klockgether, Thomas, Klopstock, Thomas, Minnerop, Martina, Münchau, Alexander, Renaud, Mathilde, Santorelli, Filippo M., Schöls, Ludger, Thieme, Andreas, and Vielhaber, Stefan

Subjects
NATURAL history, ATAXIA, HEALTH outcome assessment, SPINOCEREBELLAR ataxia, CEREBELLUM degeneration, ACTIVITIES of daily living
Abstract

Objective: The Scale for the Assessment and Rating of Ataxia (SARA) is the most widely applied clinical outcome assessment (COA) for genetic ataxias, but presents metrological and regulatory challenges. To facilitate trial planning, we characterize its responsiveness (including subitem‐level relations to ataxia severity and patient‐focused outcomes) across a large number of ataxias, and provide first natural history data for several of them. Methods: Subitem‐level correlation and distribution‐based analysis of 1,637 SARA assessments in 884 patients with autosomal recessive/early onset ataxia (370 with 2–8 longitudinal assessments) were complemented by linear mixed effects modeling to estimate progression and sample sizes. Results: Although SARA subitem responsiveness varied between ataxia severities, gait/stance showed a robust granular linear scaling across the broadest range (SARA < 25). Responsiveness was diminished by incomplete subscale use at intermediate or upper levels, nontransitions ("static periods"), and fluctuating decreases/increases. All subitems except nose‐finger showed moderate‐to‐strong correlations to activities of daily living, indicating that metric properties—not content validity—limit SARA responsiveness. SARA captured mild‐to‐moderate progression in many genotypes (eg, SYNE1‐ataxia: 0.55 points/yr, ataxia with oculomotor apraxia type 2: 1.14 points/yr, POLG‐ataxia: 1.56 points/yr), but no change in others (autosomal recessive spastic ataxia of Charlevoix‐Saguenay, COQ8A‐ataxia). Whereas sensitivity to change was optimal in mild ataxia (SARA < 10), it substantially deteriorated in advanced ataxia (SARA > 25; 2.7‐fold sample size). Use of a novel rank‐optimized SARA without subitems finger‐chase and nose‐finger reduces sample sizes by 20 to 25%. Interpretation: This study comprehensively characterizes COA properties and annualized changes of the SARA across and within a large number of ataxias. It suggests specific approaches for optimizing its responsiveness that might facilitate regulatory qualification and trial design. ANN NEUROL 2023;94:470–485 [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

13. Evolution of Clinical Outcome Measures and Biomarkers in Sporadic Adult‐Onset Degenerative Ataxia

Author

Oender, Demet, primary, Faber, Jennifer, additional, Wilke, Carlo, additional, Schaprian, Tamara, additional, Lakghomi, Asadeh, additional, Mengel, David, additional, Schöls, Ludger, additional, Traschütz, Andreas, additional, Fleszar, Zofia, additional, Dufke, Claudia, additional, Vielhaber, Stefan, additional, Machts, Judith, additional, Giordano, Ilaria, additional, Grobe‐Einsler, Marcus, additional, Klopstock, Thomas, additional, Stendel, Claudia, additional, Boesch, Sylvia, additional, Nachbauer, Wolfgang, additional, Timmann‐Braun, Dagmar, additional, Thieme, Andreas Gustafsson, additional, Kamm, Christoph, additional, Dudesek, Ales, additional, Tallaksen, Chantal, additional, Wedding, Iselin, additional, Filla, Alessandro, additional, Schmid, Matthias, additional, Synofzik, Matthis, additional, and Klockgether, Thomas, additional

Published
2023
Full Text
View/download PDF

14. Improvements in Walking Distance during Nusinersen Treatment : A Prospective 3-year SMArtCARE Registry Study

Author

Pechmann, Astrid, Behrens, Max, Dörnbrack, Katharina, Tassoni, Adrian, Wenzel, Franziska, Stein, Sabine, Vogt, Sibylle, Zöller, Daniela, Bernert, Günther, Hagenacker, Tim, Schara-Schmidt, Ulrike, Walter, Maggie C., Steinbach, Meike, Blaschek, Astrid, Baumann, Matthias, Baumgartner, Manuela, Becker, Benedikt, Flotats-Bastardas, Marina, Friese, Johannes, Günther, Rene, Hahn, Andreas, Küpper, Hanna, Johannsen, Jessika, Kamm, Christoph, Koch, Jan Christoph, Köhler, Cornelia, Kölbel, Heike, Kolzter, Kirsten, Von Moers, Arpad, Naegel, Steffen, Neuwirth, Christoph, Petri, Susanne, Rödiger, Annekathrin, Schimmel, Mareike, Schrank, Bertold, Schreiber, Gudrun, Smitka, Martin, Stadler, Christian, Steiner, Elisabeth, Stögmann, Eva, Trollmann, Regina, Türk, Matthias, Weiler, Markus, Stoltenburg, Corinna, Willichowsky, Ekkehard, Zeller, Daniel, Ziegler, Andreas, Lochmüller, Hanns, and Kirschner, Janbernd

Subjects
Neurology, Medizin, Neurology (clinical), ddc:610
Abstract

Background and objectives: Disease progression in patients with spinal muscular atrophy (SMA) has changed dramatically within the past years due to the approval of three different disease-modifying treatments. Nusinersen was the first drug to be approved for the treatment of SMA patients. Clinical trials provided data from infants with SMA type 1 and children with SMA type 2, but there is still insufficient evidence and only scarcely reported long-term experience for nusinersen treatment in ambulant patients. Here, we report data from the SMArtCARE registry of ambulant patients under nusinersen treatment with a follow-up period of up to 38 months. Methods: SMArtCARE is a disease-specific registry in Germany, Austria and Switzerland. Data are collected as real-world data during routine patient visits. Our analysis included all patients under treatment with nusinersen able to walk independently before start of treatment with focus on changes in motor function. Results: Data from 231 ambulant patients were included in the analysis. During the observation period, 31 pediatric walkers (27.2%) and 31 adult walkers (26.5%) experienced a clinically meaningful improvement of≥30 m in the 6-Minute-Walk-Test. In contrast, only five adult walkers (7.7%) showed a decline in walking distance≥30 m, and two pediatric walkers (1.8%) lost the ability to walk unassisted under treatment with nusinersen. HFMSE and RULM scores improved in pediatric and remained stable in adult patients. Conclusion: Our data demonstrate a positive effect of nusinersen treatment in most ambulant pediatric and adult SMA patients. We not only observed a stabilization of disease progression or lack of deterioration, but clinically meaningful improvements in walking distance.

Published
2023

15. The role of mutations in COL6A3 in isolated dystonia

Author

Lohmann, Katja, Schlicht, Felix, Svetel, Marina, Hinrichs, Frauke, Zittel, Simone, Graf, Julia, Lohnau, Thora, Schmidt, Alexander, Mir, Pablo, Krause, Patricia, Lang, Antony E., Jabusch, Hans-Christian, Wolters, Alexander, Kamm, Christoph, Zeuner, Kirsten E., Altenmüller, Eckart, Naz, Sadaf, Chung, Sun Ju, Kostic, Vladimir S., Münchau, Alexander, Kühn, Andrea A., Brüggemann, Norbert, and Klein, Christine

Published
2016
Full Text
View/download PDF

16. Serum creatine kinase and creatinine in adult spinal muscular atrophy under nusinersen treatment

Author

Freigang, Maren, Wurster, Claudia D., Hagenacker, Tim, Stolte, Benjamin, Weiler, Markus, Kamm, Christoph, Schreiber-Katz, Olivia, Osmanovic, Alma, Petri, Susanne, Kowski, Alexander, Meyer, Thomas, Koch, Jan C., Cordts, Isabell, Deschauer, Marcus, Lingor, Paul, Aust, Elisa, Petzold, Daniel, Ludolph, Albert C., Falkenburger, Björn, Hermann, Andreas, and Günther, René

Subjects
Adult, Male, Adolescent, Medizin, Oligonucleotides, Neurosciences. Biological psychiatry. Neuropsychiatry, physiopathology [Muscular Atrophy, Spinal], Muscular Atrophy, Spinal, Young Adult, blood [Creatinine], Humans, ddc:610, RC346-429, Creatine Kinase, Research Articles, Aged, Retrospective Studies, blood [Creatine Kinase], pharmacology [Oligonucleotides], blood [Biomarkers], drug therapy [Muscular Atrophy, Spinal], Patient Acuity, Middle Aged, Prognosis, Creatinine, blood [Muscular Atrophy, Spinal], Disease Progression, Female, Neurology. Diseases of the nervous system, diagnosis [Muscular Atrophy, Spinal], Biomarkers, RC321-571, Research Article
Abstract

Objective: To determine whether serum creatine kinase activity (CK) and serum creatinine concentration (Crn) are prognostic and predictive biomarkers for disease severity, disease progression, and nusinersen treatment effects in adult patients with 5q-associated spinal muscular atrophy (SMA). Methods: Within this retrospective, multicenter observational study in 206 adult patients with SMA, we determined clinical subtypes (SMA types, ambulatory ability) and repeatedly measured CK and Crn and examined disease severity scores (Hammersmith Functional Motor Scale Expanded, Revised Upper Limb Module, and revised Amyotrophic Lateral Sclerosis Functional Rating Scale). Patients were followed under nusinersen treatment for 18 months. Results: CK and Crn differed between clinical subtypes and correlated strongly with disease severity scores (e.g., for Hammersmith Functional Motor Scale Expanded: (CK) ρ = 0.786/ (Crn) ρ = 0.558). During the 18 months of nusinersen treatment, CK decreased (∆CK = −17.56%, p

Published
2021

17. The natural history of multiple system atrophy: a prospective European cohort study

Author

Wenning, Gregor K, Geser, Felix, Krismer, Florian, Seppi, Klaus, Duerr, Susanne, Boesch, Sylvia, Köllensperger, Martin, Goebel, Georg, Pfeiffer, Karl P, Barone, Paolo, Pellecchia, Maria Teresa, Quinn, Niall P, Koukouni, Vasiliki, Fowler, Clare J, Schrag, Anette, Mathias, Christopher J, Giladi, Nir, Gurevich, Tanya, Dupont, Erik, Ostergaard, Karen, Nilsson, Christer F, Widner, Håkan, Oertel, Wolfgang, Eggert, Karla Maria, Albanese, Alberto, del Sorbo, Francesca, Tolosa, Eduardo, Cardozo, Adriana, Deuschl, Günther, Hellriegel, Helge, Klockgether, Thomas, Dodel, Richard, Sampaio, Cristina, Coelho, Miguel, Djaldetti, Ruth, Melamed, Eldad, Gasser, Thomas, Kamm, Christoph, Meco, Giuseppe, Colosimo, Carlo, Rascol, Olivier, Meissner, Wassilios G, Tison, François, and Poewe, Werner

Published
2013
Full Text
View/download PDF

18. Clinical and genetic characteristics of sporadic adult-onset degenerative ataxia

Author

Giordano, Ilaria, Harmuth, Florian, Jacobi, Heike, Paap, Brigitte, Vielhaber, Stefan, Machts, Judith, Schöls, Ludger, Synofzik, Matthis, Sturm, Marc, Tallaksen, Chantal, Wedding, Iselin M., Boesch, Sylvia, Eigentler, Andreas, van de Warrenburg, Bart, van Gaalen, Judith, Kamm, Christoph, Dudesek, Ales, Kang, Jun-Suk, Timmann, Dagmar, Silvestri, Gabriella, Masciullo, Marcella, Klopstock, Thomas, Neuhofer, Christiane, Ganos, Christos, Filla, Alessandro, Bauer, Peter, Tezenas du Montcel, Sophie, and Klockgether, Thomas

Published
2017
Full Text
View/download PDF

19. Validity and reliability of the German multidimensional fatigue inventory in spinal muscular atrophy

Author

Binz, Camilla, primary, Osmanovic, Alma, additional, Thomas, Nele H., additional, Stolte, Benjamin, additional, Freigang, Maren, additional, Cordts, Isabell, additional, Griep, Ramona, additional, Uzelac, Zeljko, additional, Wurster, Claudia D., additional, Kamm, Christoph, additional, Siegler, Hannah A., additional, Wieselmann, Gary, additional, Hermann, Andreas, additional, Lingor, Paul, additional, Deschauer, Marcus, additional, Ludolph, Albert C., additional, Meyer, Thomas, additional, Günther, René, additional, Hagenacker, Tim, additional, Petri, Susanne, additional, and Schreiber‐Katz, Olivia, additional

Published
2022
Full Text
View/download PDF

20. Hereditary spastic paraplegia: Clinicogenetic lessons from 608 patients

Author

Schüle, Rebecca, Wiethoff, Sarah, Martus, Peter, Karle, Kathrin N., Otto, Susanne, Klebe, Stephan, Klimpe, Sven, Gallenmüller, Constanze, Kurzwelly, Delia, Henkel, Dorothea, Rimmele, Florian, Stolze, Henning, Kohl, Zacharias, Kassubek, Jan, Klockgether, Thomas, Vielhaber, Stefan, Kamm, Christoph, Klopstock, Thomas, Bauer, Peter, Züchner, Stephan, Liepelt-Scarfone, Inga, and Schöls, Ludger

Published
2016
Full Text
View/download PDF

23. The ARCA registry : a collaborative global platform for advancing trial readiness in autosomal recessive cerebellar ataxias

Author

Traschütz, Andreas, Reich, Selina, Adarmes, Astrid D, Anheim, Mathieu, Ashrafi, Mahmoud Reza, Baets, Jonathan, Basak, A Nazli, Bertini, Enrico, Brais, Bernard, Gagnon, Cynthia, Gburek-Augustat, Janina, Hanagasi, Hasmet A, Heinzmann, Anna, Horvath, Rita, De Jonghe, Peter, Kamm, Christoph, Klivenyi, Peter, Klopstock, Thomas, Minnerop, Martina, Münchau, Alexander, Renaud, Mathilde, Roxburgh, Richard H, Santorelli, Filippo M, Schirinzi, Tommaso, Sival, Deborah A, Timmann, Dagmar, Vielhaber, Stefan, Wallner, Michael, Van De Warrenburg, Bart P, Zanni, Ginevra, Zuchner, Stephan, Klockgether, Thomas, Schüle, Rebecca, Schöls, Ludger, PREPARE Consortium, Synofzik, Matthis, PREPARE Consortium, Horvath, Rita [0000-0002-9841-170X], and Apollo - University of Cambridge Repository

Subjects
ataxia, Medizin, Review, registry, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Naturgeschichte (Fach), Neurology, natural history, trial readiness, ddc:570, network, ddc:610, Human medicine, Ataxie
Abstract

Contains fulltext : 238566.pdf (Publisher’s version ) (Open Access) Autosomal recessive cerebellar ataxias (ARCAs) form an ultrarare yet expanding group of neurodegenerative multisystemic diseases affecting the cerebellum and other neurological or non-neurological systems. With the advent of targeted therapies for ARCAs, disease registries have become a precious source of real-world quantitative and qualitative data complementing knowledge from preclinical studies and clinical trials. Here, we review the ARCA Registry, a global collaborative multicenter platform (>15 countries, >30 sites) with the overarching goal to advance trial readiness in ARCAs. It presents a good clinical practice (GCP)- and general data protection regulation (GDPR)-compliant professional-reported registry for multicenter web-based capture of cross-center standardized longitudinal data. Modular electronic case report forms (eCRFs) with core, extended, and optional datasets allow data capture tailored to the participating site's variable interests and resources. The eCRFs cover all key data elements required by regulatory authorities [European Medicines Agency (EMA)] and the European Rare Disease (ERD) platform. They capture genotype, phenotype, and progression and include demographic data, biomarkers, comorbidity, medication, magnetic resonance imaging (MRI), and longitudinal clinician- or patient-reported ratings of ataxia severity, non-ataxia features, disease stage, activities of daily living, and (mental) health status. Moreover, they are aligned to major autosomal-dominant spinocerebellar ataxia (SCA) and sporadic ataxia (SPORTAX) registries in the field, thus allowing for joint and comparative analyses not only across ARCAs but also with SCAs and sporadic ataxias. The registry is at the core of a systematic multi-component ARCA database cluster with a linked biobank and an evolving study database for digital outcome measures. Currently, the registry contains more than 800 patients with almost 1,500 visits representing all ages and disease stages; 65% of patients with established genetic diagnoses capture all the main ARCA genes, and 35% with unsolved diagnoses are targets for advanced next-generation sequencing. The ARCA Registry serves as the backbone of many major European and transatlantic consortia, such as PREPARE, PROSPAX, and the Ataxia Global Initiative, with additional data input from SPORTAX. It has thus become the largest global trial-readiness registry in the ARCA field.

Published
2021

24. The ARCA Registry: a collaborative global platform for advancing trial readiness in autosomal recessive cerebellar ataxias

Author

Başak, Ayşe Nazlı (ORCID 0000-0001-9257-3540 & YÖK ID 1512), Traschuetz, Andreas; Reich, Selina; Adarmes, Astrid D.; Anheim, Mathieu; Ashrafi, Mahmoud Reza; Baets, Jonathan; Bertini, Enrico; Brais, Bernard; Gagnon, Cynthia; Gburek-Augustat, Janina; Hanagasi, Hasmet A.; Heinzmann, Anna; Horvath, Rita; de Jonghe, Peter; Kamm, Christoph; Klivenyi, Peter; Klopstock, Thomas; Minnerop, Martina; Muenchau, Alexander; Renaud, Mathilde; Roxburgh, Richard H.; Santorelli, Filippo M.; Schirinzi, Tommaso; Sival, Deborah A.; Timmann, Dagmar; Vielhaber, Stefan; Wallner, Michael; van de Warrenburg, Bart P.; Zanni, Ginevra; Zuchner, Stephan; Klockgether, Thomas; Schuele, Rebecca; Schols, Ludger; Synofzik, Matthis, Başak, Ayşe Nazlı (ORCID 0000-0001-9257-3540 & YÖK ID 1512), and Traschuetz, Andreas; Reich, Selina; Adarmes, Astrid D.; Anheim, Mathieu; Ashrafi, Mahmoud Reza; Baets, Jonathan; Bertini, Enrico; Brais, Bernard; Gagnon, Cynthia; Gburek-Augustat, Janina; Hanagasi, Hasmet A.; Heinzmann, Anna; Horvath, Rita; de Jonghe, Peter; Kamm, Christoph; Klivenyi, Peter; Klopstock, Thomas; Minnerop, Martina; Muenchau, Alexander; Renaud, Mathilde; Roxburgh, Richard H.; Santorelli, Filippo M.; Schirinzi, Tommaso; Sival, Deborah A.; Timmann, Dagmar; Vielhaber, Stefan; Wallner, Michael; van de Warrenburg, Bart P.; Zanni, Ginevra; Zuchner, Stephan; Klockgether, Thomas; Schuele, Rebecca; Schols, Ludger; Synofzik, Matthis

Abstract

Autosomal recessive cerebellar ataxias (ARCAs) form an ultrarare yet expanding group of neurodegenerative multisystemic diseases affecting the cerebellum and other neurological or non-neurological systems. With the advent of targeted therapies for ARCAs, disease registries have become a precious source of real-world quantitative and qualitative data complementing knowledge from preclinical studies and clinical trials. Here, we review the ARCA Registry, a global collaborative multicenter platform (>15 countries, >30 sites) with the overarching goal to advance trial readiness in ARCAs. It presents a good clinical practice (GCP)- and general data protection regulation (GDPR)-compliant professional-reported registry for multicenter web-based capture of cross-center standardized longitudinal data. Modular electronic case report forms (eCRFs) with core, extended, and optional datasets allow data capture tailored to the participating site's variable interests and resources. The eCRFs cover all key data elements required by regulatory authorities [European Medicines Agency (EMA)] and the European Rare Disease (ERD) platform. They capture genotype, phenotype, and progression and include demographic data, biomarkers, comorbidity, medication, magnetic resonance imaging (MRI), and longitudinal clinician- or patient-reported ratings of ataxia severity, non-ataxia features, disease stage, activities of daily living, and (mental) health status. Moreover, they are aligned to major autosomal-dominant spinocerebellar ataxia (SCA) and sporadic ataxia (SPORTAX) registries in the field, thus allowing for joint and comparative analyses not only across ARCAs but also with SCAs and sporadic ataxias. The registry is at the core of a systematic multi-component ARCA database cluster with a linked biobank and an evolving study database for digital outcome measures. Currently, the registry contains more than 800 patients with almost 1,500 visits representing all ages and disease stages; 65% of

Published
2021

25. GLUT1 mutations are a cause of paroxysmal exertion-induced dyskinesias and induce hemolytic anemia by a cation leak

Author

Weber, Yvonne G., Storch, Alexander, Wuttke, Thomas V., Brockmann, Knut, Kempfle, Judith, Maljevic, Snezana, Margari, Lucia, Kamm, Christoph, Schneider, Susanne A., Huber, Stephan M., Pekrun, Arnulf, Roebling, Robert, Seebohm, Guiscard, Koka, Saisudha, Lang, Camelia, Kraft, Eduard, Blazevic, Dragica, Salvo-Vargas, Alberto, Fauler, Michael, Mottaghy, Felix M., Munchau, Alexander, Edwards, Mark J., Presicci, Anna, Margari, Francesco, Gasser, Thomas, Lang, Florian, Bhatia, Kailash P., Lehmann-Horn, Frank, and Lerche, Holger

Subjects
Hemolytic anemia -- Risk factors, Hemolytic anemia -- Diagnosis, Gene mutations -- Research, Movement disorders -- Risk factors, Movement disorders -- Diagnosis, Movement disorders -- Care and treatment
Abstract

Paroxysmal dyskinesias are episodic movement disorders that can be inherited or are sporadic in nature. The pathophysiology underlying these disorders remains largely unknown but may involve disrupted ion homeostasis due to defects in cell-surface channels or nutrient transporters. In this study, we describe a family with paroxysmal exertion-induced dyskinesia (PED) over 3 generations. Their PED was accompanied by epilepsy, mild developmental delay, reduced CSF glucose levels, hemolytic anemia with echinocytosis, and altered erythrocyte ion concentrations. Using a candidate gene approach, we identified a causative deletion of 4 highly conserved amino acids (Q282_S285del) in the pore region of the glucose transporter 1 (GLUT1). Functional studies in Xenopus oocytes and human erythrocytes revealed that this mutation decreased glucose transport and caused a cation leak that alters intracellular concentrations of sodium, potassium, and calcium. We screened 4 additional families, in which PED is combined with epilepsy, developmental delay, or migraine, but not with hemolysis or echinocytosis, and identified 2 additional GLUT1 mutations (A275T, G314S) that decreased glucose transport but did not affect cation permeability. Combining these data with brain imaging studies, we propose that the dyskinesias result from an exertion-induced energy deficit that may cause episodic dysfunction of the basal ganglia, and that the hemolysis with echinocytosis may result from alterations in intracellular electrolytes caused by a cation leak through mutant GLUT1., Introduction Paroxysmal dyskinesias (PDs) are characterized by involuntary movements triggered by certain stimuli such as sudden movement or prolonged exercise. They are classified into paroxysmal kinesigenic dyskinesia (PKD or PKC [...]

Published
2008

27. Novel mutation in the TOR1A (DYT1) gene in atypical, early onset dystonia and polymorphisms in dystonia and early onset parkinsonism

Author

Leung, Joanne, Klein, Christine, Friedman, Jennifer, Vieregge, Peter, Jacobs, Helfried, Doheny, Dana, Kamm, Christoph, DeLeon, Deborah, Pramstaller, Peter P., Penney, John B., Eisengart, Marvin, Jankovic, Joseph, Gasser, Thomas, Bressman, Susan B., Corey, David P., Kramer, Patricia, Brin, Mitchell F., Ozelius, Laurie J., and Breakefield, Xandra O.

Published
2001
Full Text
View/download PDF

29. Prominent White Matter Involvement in Multiple System Atrophy of Cerebellar Type

Author

Faber, Jennifer, primary, Giordano, Ilaria, additional, Jiang, Xueyan, additional, Kindler, Christine, additional, Spottke, Annika, additional, Acosta‐Cabronero, Julio, additional, Nestor, Peter J., additional, Machts, Judith, additional, Düzel, Emrah, additional, Vielhaber, Stefan, additional, Speck, Oliver, additional, Dudesek, Ales, additional, Kamm, Christoph, additional, Scheef, Lukas, additional, and Klockgether, Thomas, additional

Published
2020
Full Text
View/download PDF

31. Minocycline 1-year therapy in multiple-system-atrophy: Effect on clinical symptoms and [11C] (R)-PK11195 PET (MEMSA-trial)

Author

Dodel, Richard, Spottke, Annika, Gerhard, Alexander, Reuss, Alexander, Reinecker, Sylvia, Schimke, Nicole, Trenkwalder, Claudia, Sixel-Döring, Friederike, Herting, Birgit, Kamm, Christoph, Gasser, Thomas, Sawires, Martin, Geser, Felix, Köllensperger, Martin, Seppi, Klaus, Kloss, Manja, Krause, Martin, Daniels, Christine, Deuschl, Günther, Böttger, Silke, Naumann, Markus, Lipp, Axel, Gruber, Doreen, Kupsch, Andreas, Du, Yansheng, Turkheimer, Federico, Brooks, David J., Klockgether, Thomas, Poewe, Werner, Wenning, Gregor, Schade-Brittinger, Carmen, Oertel, Wolfgang H., and Eggert, Karla

Published
2010
Full Text
View/download PDF

32. Red flags for multiple system atrophy

Author

Köllensperger, Martin, Geser, Felix, Seppi, Klaus, Stampfer-Kountchev, Michaela, Sawires, Martin, Scherfler, Christoph, Boesch, Sylvia, Mueller, Joerg, Koukouni, Vasiliki, Quinn, Niall, Pellecchia, Maria Teresa, Barone, Paolo, Schimke, Nicole, Dodel, Richard, Oertel, Wolfgang, Dupont, Erik, stergaard, Karen, Daniels, Christine, Deuschl, Günther, Gurevich, Tanya, Giladi, Nir, Coelho, Miguel, Sampaio, Cristina, Nilsson, Christer, Widner, Håkan, Sorbo, Francesca Del, Albanese, Alberto, Cardozo, Adriana, Tolosa, Eduardo, Abele, Michael, Klockgether, Thomas, Kamm, Christoph, Gasser, Thomas, Djaldetti, Ruth, Colosimo, Carlo, Meco, Giuseppe, Schrag, Anette, Poewe, Werner, and Wenning, Gregor K.

Published
2008
Full Text
View/download PDF

36. UCHL-1 gene in multiple system atrophy: A haplotype tagging approach

Author

Healy, Daniel G., Abou-Sleiman, Patrick M., Quinn, Niall, Ahmadi, Kourosh R., Ozawa, Tetsutaro, Kamm, Christoph, Wullner, Ullrich, Oertel, Wolfgang H., Burk, Katrin, Dupont, Erik, Pellecchia, Maria T., Tolosa, Eduardo, Gasser, Thomas, Holton, Janice L., Revesz, Tamas, Goldstein, David B., Lees, Andrew J., and Wood, Nicholas W.

Published
2005
Full Text
View/download PDF

38. Long-Term Effect of GPi-DBS in a Patient With Generalized Dystonia Due to GLUT1 Deficiency Syndrome

Author

Hanci, Idil, Kamm, Christoph, Scholten, Marlieke, Roncoroni, Lorenzo P, Weber, Yvonne, Krüger, Rejko, Plewnia, Christian, Gharabaghi, Alireza, and Weiss, Daniel

Subjects
glucose transporter type-1 deficiency syndrome (GLUT1-DS), globus pallidus internus (GPi), Neurology, glucose transporter type 1 (GLUT1), Case Report, ddc:610, dystonia, deep brain stimulation (DBS), nervous system diseases
Abstract

Treatment outcomes from pallidal deep brain stimulation are highly heterogeneous reflecting the phenotypic and etiologic spectrum of dystonia. Treatment stratification to neurostimulation therapy primarily relies on the phenotypic motor presentation; however, etiology including genetic factors are increasingly recognized as modifiers of treatment outcomes. Here, we describe a 53 year-old female patient with a progressive generalized dystonia since age 25. The patient underwent deep brain stimulation of the globus pallidus internus (GPi-DBS) at age 44. Since the clinical phenotype included mobile choreo-dystonic features, we expected favorable therapeutic outcome from GPi-DBS. Although mobile dystonia components were slightly improved in the long-term outcome from GPi-DBS the overall therapeutic response 9 years from implantation was limited when comparing 'stimulation off' and 'stimulation on' despite of proper electrode localization and sufficient stimulation programming. In order to further understand the reason for this limited motor symptom response, we aimed to clarify the etiology of generalized dystonia in this patient. Genetic testing identified a novel heterozygous pathogenic SLC2A1 mutation as cause of glucose transporter type 1 deficiency syndrome (GLUT1-DS). This case report presents the first outcome of GPi-DBS in a patient with GLUT1-DS, and suggests that genotype relations may increasingly complement phenotype-based therapy stratification of GPi-DBS in dystonia.

Published
2018

39. Patient-Reported Prevalence of Non-motor Symptoms Is Low in Adult Patients Suffering From 5q Spinal Muscular Atrophy

Author

Günther, René, primary, Wurster, Claudia Diana, additional, Cordts, Isabell, additional, Koch, Jan Christoph, additional, Kamm, Christoph, additional, Petzold, Daniel, additional, Aust, Elisa, additional, Deschauer, Marcus, additional, Lingor, Paul, additional, Ludolph, Albert Christian, additional, and Hermann, Andreas, additional

Published
2019
Full Text
View/download PDF

40. Validation of a self‐completed Dystonia Non‐Motor Symptoms Questionnaire

Author

Klingelhoefer, Lisa, primary, Chaudhuri, Kallol R., additional, Kamm, Christoph, additional, Martinez‐Martin, Pablo, additional, Bhatia, Kailash, additional, Sauerbier, Anna, additional, Kaiser, Maximilian, additional, Rodriguez‐Blazquez, Carmen, additional, Balint, Bettina, additional, Untucht, Robert, additional, Hall, Lynsey J., additional, Mildenstein, Lauritz, additional, Wienecke, Miriam, additional, Martino, Davide, additional, Gregor, Olaf, additional, Storch, Alexander, additional, and Reichmann, Heinz, additional

Published
2019
Full Text
View/download PDF

41. Loss of paraplegin drives spasticity rather than ataxia in a cohort of 241 patients with SPG7

Author

Coarelli, Giulia, Schule, Rebecca, van de Warrenburg, Bart P C, De Jonghe, Peter, Ewenczyk, Claire, Martinuzzi, Andrea, Synofzik, Matthis, Hamer, Elisa E.G., Baets, Jonathan, Anheim, Mathieu, Schöls, Lüdger, Deconinck, Tine, Masrori, Pegah, Fontaine, Bertrand, Klockgether, Thomas, D'Angelo, Maria Grazia, Monin, Marie Lorraine, De Bleecker, Jan, Migeotte, Isabelle, Charles, Perrine, Bassi, Maria Teresa, Klopstock, Thomas, Mochel, Fanny, Ollagnon-Roman, Elisabeth, D'Hooghe, Marc, Kamm, Christoph, Kurzwelly, Delia, Papin, Melanie, Davoine, Claire Sophie, Banneau, Guillaume, du Montcel, Sophie Tezenas, Seilhean, Danielle, Brice, Alexis, Duyckaerts, Charles, Stevanin, Giovanni, Dürr, Alexandra, Coarelli, Giulia, Schule, Rebecca, van de Warrenburg, Bart P C, De Jonghe, Peter, Ewenczyk, Claire, Martinuzzi, Andrea, Synofzik, Matthis, Hamer, Elisa E.G., Baets, Jonathan, Anheim, Mathieu, Schöls, Lüdger, Deconinck, Tine, Masrori, Pegah, Fontaine, Bertrand, Klockgether, Thomas, D'Angelo, Maria Grazia, Monin, Marie Lorraine, De Bleecker, Jan, Migeotte, Isabelle, Charles, Perrine, Bassi, Maria Teresa, Klopstock, Thomas, Mochel, Fanny, Ollagnon-Roman, Elisabeth, D'Hooghe, Marc, Kamm, Christoph, Kurzwelly, Delia, Papin, Melanie, Davoine, Claire Sophie, Banneau, Guillaume, du Montcel, Sophie Tezenas, Seilhean, Danielle, Brice, Alexis, Duyckaerts, Charles, Stevanin, Giovanni, and Dürr, Alexandra

Abstract

Objective: We took advantage of a large multinational recruitment to delineate genotype-phenotype correlations in a large, trans-European multicenter cohort of patients with spastic paraplegia gene 7 (SPG7). Methods: We analyzed clinical and genetic data from 241 patients with SPG7, integrating neurologic follow-up data. One case was examined neuropathologically. Results: Patients with SPG7 had a mean age of 35.5 ± 14.3 years (n = 233) at onset and presented with spasticity (n = 89), ataxia (n = 74), or both (n = 45). At the first visit, patients with a longer disease duration (>20 years, n = 62) showed more cerebellar dysarthria (p < 0.05), deep sensory loss (p < 0.01), muscle wasting (p < 0.01), ophthalmoplegia (p < 0.05), and sphincter dysfunction (p < 0.05) than those with a shorter duration (<10 years, n = 93). Progression, measured by Scale for the Assessment and Rating of Ataxia evaluations, showed a mean annual increase of 1.0 ± 1.4 points in a subgroup of 30 patients. Patients homozygous for loss of function (LOF) variants (n = 65) presented significantly more often with pyramidal signs (p < 0.05), diminished visual acuity due to optic atrophy (p < 0.0001), and deep sensory loss (p < 0.0001) than those with at least 1 missense variant (n = 176). Patients with at least 1 Ala510Val variant (58%) were older (age 37.6 ± 13.7 vs 32.8 ± 14.6 years, p < 0.05) and showed ataxia at onset (p < 0.05). Neuropathologic examination revealed reduction of the pyramidal tract in the medulla oblongata and moderate loss of Purkinje cells and substantia nigra neurons. Conclusions: This is the largest SPG7 cohort study to date and shows a spasticity-predominant phenotype of LOF variants and more frequent cerebellar ataxia and later onset in patients carrying at least 1 Ala510Val variant., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2018

42. Early onset torsion dystonia (Oppenheim's dystonia)

Author

Kamm Christoph

Subjects
Medicine
Abstract

Abstract Early onset torsion dystonia (EOTD) is a rare movement disorder characterized by involuntary, repetitive, sustained muscle contractions or postures involving one or more sites of the body. A US study estimated the prevalence at approximately 1 in 30,000. The estimated prevalence in the general population of Europe seems to be lower, ranging from 1 in 330,000 to 1 in 200,000, although precise numbers are currently not available. The estimated prevalence in the Ashkenazi Jewish population is approximately five to ten times higher, due to a founder mutation. Symptoms of EOTD typically develop first in an arm or leg in middle to late childhood and progress in approximately 30% of patients to other body regions (generalized dystonia) within about five years. Distribution and severity of symptoms vary widely between affected individuals. The majority of cases from various ethnic groups are caused by an autosomal dominantly inherited deletion of 3 bp (GAG) in the DYT1 gene on chromosome 9q34. This gene encodes a protein named torsinA, which is presumed to act as a chaperone protein associated with the endoplasmic reticulum and the nuclear envelope. It may interact with the dopamine transporter and participate in intracellular trafficking, although its precise function within the cell remains to be determined. Molecular genetic diagnostic and genetic counseling is recommended for individuals with age of onset below 26 years, and may also be considered in those with onset after 26 years having a relative with typical early onset dystonia. Treatment options include botulinum toxin injections for focal symptoms, pharmacological therapy such as anticholinergics (most commonly trihexiphenydil) for generalized dystonia and surgical approaches such as deep brain stimulation of the internal globus pallidus or intrathecal baclofen application in severe cases. All patients have normal cognitive function, and despite a high rate of generalization of dystonia, 75% of those patients are able to maintain ambulation and independence, and therefore a comparatively good quality of life, with modern treatment modalities.

Published
2006
Full Text
View/download PDF

43. Zervikale Dystonien

Author

Reichel, Gerhard, additional, Kamm, Christoph, additional, Kang, Jun Suk, additional, Müngersdorf, Martina, additional, Paus, Sebastian, additional, Reuter, Iris, additional, Stenner, Andrea, additional, and Weise, David, additional

Published
2018
Full Text
View/download PDF

44. Development and validation of the Unified Multiple System Atrophy Rating Scale (UMSARS)

Author

Wenning, Gregor K., Tison, François, Seppi, Klaus, Sampiao, Cristina, Diem, Anja, Yekhlef, Farid, Ghorayeb, Imad, Ory, Fabienne, Galitzky, Monique, Scaravilli, Tommaso, Bozi, Maria, Colosimo, Carlo, Gilman, Sid, Shults, Clifford W., Quinn, Niall P., Rascol, Olivier, Poewe, Werner, Dupont, Erik, Ostergaard, Karen, Tolosa, Eduardo, Klockgether, Thomas, Dodel, Richard, Abele, Michael, Pollak, Pierre, Geser, Felix, Stamfer, Michaela, Deuschl, Günther, Daniels, Christine, Coelho, Miguel, Pirtosek, Zvezdan, Brooks, David J., Fowler, Claire, Lees, Andrew, Mathias, Christopher J., Revesz, Tamas, Gerhard, Alexander, Holton, Janice, Schrag, Anette, Wood, Nick, Lindvall, Olle, Widner, Håkan, Grabowski, Martin, Nilsson, Christer F., Oertel, Wolfgang, Eggert, Karla Maria, Schimke, Nicole, Albanese, Alberto, del Sorbo, Francesco, Barone, Paolo, Carella, Francesco, Djaljetti, Ruth, Meco, Giuseppe, Berciano, Jose, Gonzalez-Mandly, Andres, Giladi, Nir, Gurevich, Tanya, Gasser, Thomas, Kamm, Christoph, Aquilonius, Sten Magnus, and Bergquist, Jonas

Subjects
Male, Gerontology, medicine.medical_specialty, Cerebellar Ataxia, Scale (ratio), education, Autonomic Nervous System, Severity of Illness Index, Speech Disorders, Part iii, Disability Evaluation, Hypotension, Orthostatic, Atrophy, Physical medicine and rehabilitation, Erectile Dysfunction, Parkinsonian Disorders, Rating scale, Surveys and Questionnaires, Internal consistency, Activities of Daily Living, Validation, medicine, Humans, Interrater Reliability, Age of Onset, Observer Variation, Reproducibility of Results, Multiple System Atrophy, Urinary Retention, Unified Multiple System Atrophy Rating Scale, medicine.disease, Degree (music), Inter-rater reliability, Urinary Incontinence, Neurology, Female, International Cooperative Ataxia Rating Scale, Neurology (clinical), Psychology
Abstract

We aimed to develop and validate a novel rating scale for multiple system atrophy (Unified Multiple System Atrophy Rating Scale - UMSARS). The scale comprises the following components: Part I, historical, 12 items; Part II, motor examination, 14 items; Part III, autonomic examination; and Part IV, global disability scale. For validation purposes, 40 MSA patients were assessed in four centers by 4 raters per center (2 senior and 2 junior raters). The raters applied the UMSARS, as well as a range of other scales, including the Unified Parkinson's Disease Rating Scale (UPDRS) and the International Cooperative Ataxia Rating Scale (ICARS). Internal consistency was high for both UMSARS-1 (Crohnbach's alpha = 0.84) and UMSARS-II (Crohnbach's alpha = 0.90) sections. The interrater reliability of most of the UMSARS-I and -II items as well as of total UMSARS-I and -II subscores was substantial (k (w) = 0.6-0.8) to excellent (k (w) > 0.8). UMSARS-II correlated well with UPDRS-III and ICARS (rs > 0.8). Depending on the degree of the patient's disability, completion of the entire UMSARS took 30 to 45 minutes. Based on our findings, the UMSARS appears to be a multidimensional, reliable, and valid scale for semiquantitative clinical assessments of MSA patients.

Published
2004

49. Minocycline 1-year therapy in multiple-system-atrophy: effect on clinical symptoms and [(11)C] (R)-PK11195 PET (MEMSA-trial)

Author

Dodel, Richard, Spottke, Annika, Gerhard, Alexander, Reuss, Alexander, Reinecker, Sylvia, Schimke, Nicole, Trenkwalder, Claudia, Sixel-Döring, Friederike, Herting, Birgit, Kamm, Christoph, Gasser, Thomas, Sawires, Martin, Geser, Felix, Köllensperger, Martin, Seppi, Klaus, Kloss, Manja, Krause, Martin, Daniels, Christine, Deuschl, Günther, Böttger, Silke, Naumann, Markus, Lipp, Axel, Gruber, Doreen, Kupsch, Andreas, Du, Yansheng, Turkheimer, Federico, Brooks, David J., Klockgether, Thomas, Poewe, Werner, Wenning, Gregor, Schade-Brittinger, Carmen, Oertel, Wolfgang H., and Eggert, Karla

Subjects
Adult, Male, Time Factors, Minocycline, Middle Aged, Multiple System Atrophy, Isoquinolines, Magnetic Resonance Imaging, Severity of Illness Index, Statistics, Nonparametric, Neuroprotective Agents, Treatment Outcome, Double-Blind Method, Positron-Emission Tomography, Quality of Life, Humans, Female, Aged, Follow-Up Studies
Abstract

The aim of the study was to investigate the efficacy of the antibiotic minocycline as a drug treatment in patients with Multiple-System-Atrophy Parkinson-type (MSA-P). Sixty-three patients were randomized to minocycline 200 mg/d (n = 32) or a matching placebo (n = 31). The primary outcome variable was the change in the value of the motor score of the Unified Multiple-System-Atrophy Rating-Scale (UMSARSII) from baseline to 48 weeks. Secondary outcome variables included subscores and individual Parkinsonian symptoms as determined by the UMSARS and the Unified-Parkinson's-Disease Rating-Scale (UPDRS). Health-related quality of life (HrQoL) was assessed using the EQ-5D and SF-12. "Progression rate" was assumed to be reflected in the change in motor function over 48 weeks. At 24 weeks and 48 weeks of follow-up, there was a significant deterioration in motor scores in both groups, but neither the change in UMSARSII nor in UPDRSIII differed significantly between treatment groups, i.e. "progression rate" was considered to be similar in both treatment arms. HrQoL did not differ among the two treatment arms. In a small subgroup of patients (n = 8; minocycline = 3, placebo = 5)[(11)C](R)-PK11195-PET was performed. The three patients in the minocycline group had an attenuated mean increase in microglial activation as compared to the placebo group (P = 0.07) and in two of them individually showed decreased [11C](R)-PK11195 binding actually decreased. These preliminary PET-data suggest that minocycline may interfere with microglial activation. The relevance of this observation requires further investigation. This prospective, 48 week, randomized, double-blind, multinational study failed to show a clinical effect of minocycline on symptom severity as assessed by clinical motor function.

Published
2009

Catalog

Books, media, physical & digital resources
See catalog results