September 05, 2017; 89 (10) Article
Clinical and genetic characteristics of sporadic adult-onset degenerative ataxia
Ilaria Giordano, Florian Harmuth, Heike Jacobi, Brigitte Paap, Stefan Vielhaber, Judith Machts, Ludger Schöls, Matthis Synofzik, Marc Sturm, Chantal Tallaksen, Iselin M. Wedding, Sylvia Boesch, Andreas Eigentler, Bart van de Warrenburg, Judith van Gaalen, Christoph Kamm, Ales Dudesek, Jun-Suk Kang, Dagmar Timmann, Gabriella Silvestri, Marcella Masciullo, Thomas Klopstock, Christiane Neuhofer, Christos Ganos, Alessandro Filla, Peter Bauer, Sophie Tezenas du Montcel, Thomas Klockgether
First published August 9, 2017, DOI: https://doi.org/10.1212/WNL.0000000000004311
Ilaria Giordano
From the Department of Neurology (I.G., T.K.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G., H.J., B.P., T.K.), Bonn; Institute of Medical Genetics and Applied Genomics (F.H., M.S.) and Department of Neurodegenerative Diseases (L.S., M.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (H.J.), Heidelberg University Hospital; Department of Neurology (S.V.), Otto-von-Guericke University Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (S.V., J.M.), Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (L.S., M.S.), Tübingen, Germany; Department of Neurology (C.T., I.M.W.), Oslo University Hospital; Faculty of Medicine (C.T.), Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology (S.B., A.E.), Medical University Innsbruck, Austria; Department of Neurology (B.v.d.W., J.v.G.), Radboud University Medical Center, Nijmegen, Netherlands; Department of Neurology (C.K., A.D.), University of Rostock; German Center for Neurodegenerative Diseases (DZNE) (C.K., A.D.), Rostock; Department of Neurology (J.-S.K.), University of Frankfurt; Department of Neurology (D.T.), Essen University Hospital, University of Duisburg-Essen, Germany; Institute of Neurology (G.S.), Catholic University of Sacred Heart; SPInal REhabilitation Lab (SPIRE) (M.M.), Fondazione Santa Lucia, IRCCS, Rome, Italy; Department of Neurology (T.K., C.N.), Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich; German Center for Neurodegenerative Diseases (DZNE) (T.K., C.N.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich; Department of Neurology (C.G.), University Medical Center Hamburg-Eppendorf (UKE), Germany; Department of Neuroscience and Reproductive and Odontostomatological Sciences (A.F.), Federico II University, Naples, Italy; Centogene AG (P.B.), Rostock, Germany; Pierre Louis Institute of Epidemiology and Public Health (S.T.d.M.), Pierre and Marie Curie University (UPMC); and AP-HP (S.T.d.M.), Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Florian Harmuth
From the Department of Neurology (I.G., T.K.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G., H.J., B.P., T.K.), Bonn; Institute of Medical Genetics and Applied Genomics (F.H., M.S.) and Department of Neurodegenerative Diseases (L.S., M.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (H.J.), Heidelberg University Hospital; Department of Neurology (S.V.), Otto-von-Guericke University Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (S.V., J.M.), Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (L.S., M.S.), Tübingen, Germany; Department of Neurology (C.T., I.M.W.), Oslo University Hospital; Faculty of Medicine (C.T.), Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology (S.B., A.E.), Medical University Innsbruck, Austria; Department of Neurology (B.v.d.W., J.v.G.), Radboud University Medical Center, Nijmegen, Netherlands; Department of Neurology (C.K., A.D.), University of Rostock; German Center for Neurodegenerative Diseases (DZNE) (C.K., A.D.), Rostock; Department of Neurology (J.-S.K.), University of Frankfurt; Department of Neurology (D.T.), Essen University Hospital, University of Duisburg-Essen, Germany; Institute of Neurology (G.S.), Catholic University of Sacred Heart; SPInal REhabilitation Lab (SPIRE) (M.M.), Fondazione Santa Lucia, IRCCS, Rome, Italy; Department of Neurology (T.K., C.N.), Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich; German Center for Neurodegenerative Diseases (DZNE) (T.K., C.N.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich; Department of Neurology (C.G.), University Medical Center Hamburg-Eppendorf (UKE), Germany; Department of Neuroscience and Reproductive and Odontostomatological Sciences (A.F.), Federico II University, Naples, Italy; Centogene AG (P.B.), Rostock, Germany; Pierre Louis Institute of Epidemiology and Public Health (S.T.d.M.), Pierre and Marie Curie University (UPMC); and AP-HP (S.T.d.M.), Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Heike Jacobi
From the Department of Neurology (I.G., T.K.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G., H.J., B.P., T.K.), Bonn; Institute of Medical Genetics and Applied Genomics (F.H., M.S.) and Department of Neurodegenerative Diseases (L.S., M.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (H.J.), Heidelberg University Hospital; Department of Neurology (S.V.), Otto-von-Guericke University Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (S.V., J.M.), Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (L.S., M.S.), Tübingen, Germany; Department of Neurology (C.T., I.M.W.), Oslo University Hospital; Faculty of Medicine (C.T.), Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology (S.B., A.E.), Medical University Innsbruck, Austria; Department of Neurology (B.v.d.W., J.v.G.), Radboud University Medical Center, Nijmegen, Netherlands; Department of Neurology (C.K., A.D.), University of Rostock; German Center for Neurodegenerative Diseases (DZNE) (C.K., A.D.), Rostock; Department of Neurology (J.-S.K.), University of Frankfurt; Department of Neurology (D.T.), Essen University Hospital, University of Duisburg-Essen, Germany; Institute of Neurology (G.S.), Catholic University of Sacred Heart; SPInal REhabilitation Lab (SPIRE) (M.M.), Fondazione Santa Lucia, IRCCS, Rome, Italy; Department of Neurology (T.K., C.N.), Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich; German Center for Neurodegenerative Diseases (DZNE) (T.K., C.N.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich; Department of Neurology (C.G.), University Medical Center Hamburg-Eppendorf (UKE), Germany; Department of Neuroscience and Reproductive and Odontostomatological Sciences (A.F.), Federico II University, Naples, Italy; Centogene AG (P.B.), Rostock, Germany; Pierre Louis Institute of Epidemiology and Public Health (S.T.d.M.), Pierre and Marie Curie University (UPMC); and AP-HP (S.T.d.M.), Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Brigitte Paap
From the Department of Neurology (I.G., T.K.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G., H.J., B.P., T.K.), Bonn; Institute of Medical Genetics and Applied Genomics (F.H., M.S.) and Department of Neurodegenerative Diseases (L.S., M.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (H.J.), Heidelberg University Hospital; Department of Neurology (S.V.), Otto-von-Guericke University Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (S.V., J.M.), Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (L.S., M.S.), Tübingen, Germany; Department of Neurology (C.T., I.M.W.), Oslo University Hospital; Faculty of Medicine (C.T.), Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology (S.B., A.E.), Medical University Innsbruck, Austria; Department of Neurology (B.v.d.W., J.v.G.), Radboud University Medical Center, Nijmegen, Netherlands; Department of Neurology (C.K., A.D.), University of Rostock; German Center for Neurodegenerative Diseases (DZNE) (C.K., A.D.), Rostock; Department of Neurology (J.-S.K.), University of Frankfurt; Department of Neurology (D.T.), Essen University Hospital, University of Duisburg-Essen, Germany; Institute of Neurology (G.S.), Catholic University of Sacred Heart; SPInal REhabilitation Lab (SPIRE) (M.M.), Fondazione Santa Lucia, IRCCS, Rome, Italy; Department of Neurology (T.K., C.N.), Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich; German Center for Neurodegenerative Diseases (DZNE) (T.K., C.N.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich; Department of Neurology (C.G.), University Medical Center Hamburg-Eppendorf (UKE), Germany; Department of Neuroscience and Reproductive and Odontostomatological Sciences (A.F.), Federico II University, Naples, Italy; Centogene AG (P.B.), Rostock, Germany; Pierre Louis Institute of Epidemiology and Public Health (S.T.d.M.), Pierre and Marie Curie University (UPMC); and AP-HP (S.T.d.M.), Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Stefan Vielhaber
From the Department of Neurology (I.G., T.K.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G., H.J., B.P., T.K.), Bonn; Institute of Medical Genetics and Applied Genomics (F.H., M.S.) and Department of Neurodegenerative Diseases (L.S., M.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (H.J.), Heidelberg University Hospital; Department of Neurology (S.V.), Otto-von-Guericke University Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (S.V., J.M.), Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (L.S., M.S.), Tübingen, Germany; Department of Neurology (C.T., I.M.W.), Oslo University Hospital; Faculty of Medicine (C.T.), Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology (S.B., A.E.), Medical University Innsbruck, Austria; Department of Neurology (B.v.d.W., J.v.G.), Radboud University Medical Center, Nijmegen, Netherlands; Department of Neurology (C.K., A.D.), University of Rostock; German Center for Neurodegenerative Diseases (DZNE) (C.K., A.D.), Rostock; Department of Neurology (J.-S.K.), University of Frankfurt; Department of Neurology (D.T.), Essen University Hospital, University of Duisburg-Essen, Germany; Institute of Neurology (G.S.), Catholic University of Sacred Heart; SPInal REhabilitation Lab (SPIRE) (M.M.), Fondazione Santa Lucia, IRCCS, Rome, Italy; Department of Neurology (T.K., C.N.), Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich; German Center for Neurodegenerative Diseases (DZNE) (T.K., C.N.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich; Department of Neurology (C.G.), University Medical Center Hamburg-Eppendorf (UKE), Germany; Department of Neuroscience and Reproductive and Odontostomatological Sciences (A.F.), Federico II University, Naples, Italy; Centogene AG (P.B.), Rostock, Germany; Pierre Louis Institute of Epidemiology and Public Health (S.T.d.M.), Pierre and Marie Curie University (UPMC); and AP-HP (S.T.d.M.), Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Judith Machts
From the Department of Neurology (I.G., T.K.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G., H.J., B.P., T.K.), Bonn; Institute of Medical Genetics and Applied Genomics (F.H., M.S.) and Department of Neurodegenerative Diseases (L.S., M.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (H.J.), Heidelberg University Hospital; Department of Neurology (S.V.), Otto-von-Guericke University Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (S.V., J.M.), Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (L.S., M.S.), Tübingen, Germany; Department of Neurology (C.T., I.M.W.), Oslo University Hospital; Faculty of Medicine (C.T.), Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology (S.B., A.E.), Medical University Innsbruck, Austria; Department of Neurology (B.v.d.W., J.v.G.), Radboud University Medical Center, Nijmegen, Netherlands; Department of Neurology (C.K., A.D.), University of Rostock; German Center for Neurodegenerative Diseases (DZNE) (C.K., A.D.), Rostock; Department of Neurology (J.-S.K.), University of Frankfurt; Department of Neurology (D.T.), Essen University Hospital, University of Duisburg-Essen, Germany; Institute of Neurology (G.S.), Catholic University of Sacred Heart; SPInal REhabilitation Lab (SPIRE) (M.M.), Fondazione Santa Lucia, IRCCS, Rome, Italy; Department of Neurology (T.K., C.N.), Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich; German Center for Neurodegenerative Diseases (DZNE) (T.K., C.N.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich; Department of Neurology (C.G.), University Medical Center Hamburg-Eppendorf (UKE), Germany; Department of Neuroscience and Reproductive and Odontostomatological Sciences (A.F.), Federico II University, Naples, Italy; Centogene AG (P.B.), Rostock, Germany; Pierre Louis Institute of Epidemiology and Public Health (S.T.d.M.), Pierre and Marie Curie University (UPMC); and AP-HP (S.T.d.M.), Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Ludger Schöls
From the Department of Neurology (I.G., T.K.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G., H.J., B.P., T.K.), Bonn; Institute of Medical Genetics and Applied Genomics (F.H., M.S.) and Department of Neurodegenerative Diseases (L.S., M.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (H.J.), Heidelberg University Hospital; Department of Neurology (S.V.), Otto-von-Guericke University Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (S.V., J.M.), Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (L.S., M.S.), Tübingen, Germany; Department of Neurology (C.T., I.M.W.), Oslo University Hospital; Faculty of Medicine (C.T.), Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology (S.B., A.E.), Medical University Innsbruck, Austria; Department of Neurology (B.v.d.W., J.v.G.), Radboud University Medical Center, Nijmegen, Netherlands; Department of Neurology (C.K., A.D.), University of Rostock; German Center for Neurodegenerative Diseases (DZNE) (C.K., A.D.), Rostock; Department of Neurology (J.-S.K.), University of Frankfurt; Department of Neurology (D.T.), Essen University Hospital, University of Duisburg-Essen, Germany; Institute of Neurology (G.S.), Catholic University of Sacred Heart; SPInal REhabilitation Lab (SPIRE) (M.M.), Fondazione Santa Lucia, IRCCS, Rome, Italy; Department of Neurology (T.K., C.N.), Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich; German Center for Neurodegenerative Diseases (DZNE) (T.K., C.N.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich; Department of Neurology (C.G.), University Medical Center Hamburg-Eppendorf (UKE), Germany; Department of Neuroscience and Reproductive and Odontostomatological Sciences (A.F.), Federico II University, Naples, Italy; Centogene AG (P.B.), Rostock, Germany; Pierre Louis Institute of Epidemiology and Public Health (S.T.d.M.), Pierre and Marie Curie University (UPMC); and AP-HP (S.T.d.M.), Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Matthis Synofzik
From the Department of Neurology (I.G., T.K.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G., H.J., B.P., T.K.), Bonn; Institute of Medical Genetics and Applied Genomics (F.H., M.S.) and Department of Neurodegenerative Diseases (L.S., M.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (H.J.), Heidelberg University Hospital; Department of Neurology (S.V.), Otto-von-Guericke University Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (S.V., J.M.), Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (L.S., M.S.), Tübingen, Germany; Department of Neurology (C.T., I.M.W.), Oslo University Hospital; Faculty of Medicine (C.T.), Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology (S.B., A.E.), Medical University Innsbruck, Austria; Department of Neurology (B.v.d.W., J.v.G.), Radboud University Medical Center, Nijmegen, Netherlands; Department of Neurology (C.K., A.D.), University of Rostock; German Center for Neurodegenerative Diseases (DZNE) (C.K., A.D.), Rostock; Department of Neurology (J.-S.K.), University of Frankfurt; Department of Neurology (D.T.), Essen University Hospital, University of Duisburg-Essen, Germany; Institute of Neurology (G.S.), Catholic University of Sacred Heart; SPInal REhabilitation Lab (SPIRE) (M.M.), Fondazione Santa Lucia, IRCCS, Rome, Italy; Department of Neurology (T.K., C.N.), Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich; German Center for Neurodegenerative Diseases (DZNE) (T.K., C.N.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich; Department of Neurology (C.G.), University Medical Center Hamburg-Eppendorf (UKE), Germany; Department of Neuroscience and Reproductive and Odontostomatological Sciences (A.F.), Federico II University, Naples, Italy; Centogene AG (P.B.), Rostock, Germany; Pierre Louis Institute of Epidemiology and Public Health (S.T.d.M.), Pierre and Marie Curie University (UPMC); and AP-HP (S.T.d.M.), Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Marc Sturm
From the Department of Neurology (I.G., T.K.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G., H.J., B.P., T.K.), Bonn; Institute of Medical Genetics and Applied Genomics (F.H., M.S.) and Department of Neurodegenerative Diseases (L.S., M.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (H.J.), Heidelberg University Hospital; Department of Neurology (S.V.), Otto-von-Guericke University Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (S.V., J.M.), Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (L.S., M.S.), Tübingen, Germany; Department of Neurology (C.T., I.M.W.), Oslo University Hospital; Faculty of Medicine (C.T.), Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology (S.B., A.E.), Medical University Innsbruck, Austria; Department of Neurology (B.v.d.W., J.v.G.), Radboud University Medical Center, Nijmegen, Netherlands; Department of Neurology (C.K., A.D.), University of Rostock; German Center for Neurodegenerative Diseases (DZNE) (C.K., A.D.), Rostock; Department of Neurology (J.-S.K.), University of Frankfurt; Department of Neurology (D.T.), Essen University Hospital, University of Duisburg-Essen, Germany; Institute of Neurology (G.S.), Catholic University of Sacred Heart; SPInal REhabilitation Lab (SPIRE) (M.M.), Fondazione Santa Lucia, IRCCS, Rome, Italy; Department of Neurology (T.K., C.N.), Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich; German Center for Neurodegenerative Diseases (DZNE) (T.K., C.N.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich; Department of Neurology (C.G.), University Medical Center Hamburg-Eppendorf (UKE), Germany; Department of Neuroscience and Reproductive and Odontostomatological Sciences (A.F.), Federico II University, Naples, Italy; Centogene AG (P.B.), Rostock, Germany; Pierre Louis Institute of Epidemiology and Public Health (S.T.d.M.), Pierre and Marie Curie University (UPMC); and AP-HP (S.T.d.M.), Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Chantal Tallaksen
From the Department of Neurology (I.G., T.K.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G., H.J., B.P., T.K.), Bonn; Institute of Medical Genetics and Applied Genomics (F.H., M.S.) and Department of Neurodegenerative Diseases (L.S., M.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (H.J.), Heidelberg University Hospital; Department of Neurology (S.V.), Otto-von-Guericke University Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (S.V., J.M.), Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (L.S., M.S.), Tübingen, Germany; Department of Neurology (C.T., I.M.W.), Oslo University Hospital; Faculty of Medicine (C.T.), Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology (S.B., A.E.), Medical University Innsbruck, Austria; Department of Neurology (B.v.d.W., J.v.G.), Radboud University Medical Center, Nijmegen, Netherlands; Department of Neurology (C.K., A.D.), University of Rostock; German Center for Neurodegenerative Diseases (DZNE) (C.K., A.D.), Rostock; Department of Neurology (J.-S.K.), University of Frankfurt; Department of Neurology (D.T.), Essen University Hospital, University of Duisburg-Essen, Germany; Institute of Neurology (G.S.), Catholic University of Sacred Heart; SPInal REhabilitation Lab (SPIRE) (M.M.), Fondazione Santa Lucia, IRCCS, Rome, Italy; Department of Neurology (T.K., C.N.), Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich; German Center for Neurodegenerative Diseases (DZNE) (T.K., C.N.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich; Department of Neurology (C.G.), University Medical Center Hamburg-Eppendorf (UKE), Germany; Department of Neuroscience and Reproductive and Odontostomatological Sciences (A.F.), Federico II University, Naples, Italy; Centogene AG (P.B.), Rostock, Germany; Pierre Louis Institute of Epidemiology and Public Health (S.T.d.M.), Pierre and Marie Curie University (UPMC); and AP-HP (S.T.d.M.), Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Iselin M. Wedding
From the Department of Neurology (I.G., T.K.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G., H.J., B.P., T.K.), Bonn; Institute of Medical Genetics and Applied Genomics (F.H., M.S.) and Department of Neurodegenerative Diseases (L.S., M.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (H.J.), Heidelberg University Hospital; Department of Neurology (S.V.), Otto-von-Guericke University Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (S.V., J.M.), Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (L.S., M.S.), Tübingen, Germany; Department of Neurology (C.T., I.M.W.), Oslo University Hospital; Faculty of Medicine (C.T.), Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology (S.B., A.E.), Medical University Innsbruck, Austria; Department of Neurology (B.v.d.W., J.v.G.), Radboud University Medical Center, Nijmegen, Netherlands; Department of Neurology (C.K., A.D.), University of Rostock; German Center for Neurodegenerative Diseases (DZNE) (C.K., A.D.), Rostock; Department of Neurology (J.-S.K.), University of Frankfurt; Department of Neurology (D.T.), Essen University Hospital, University of Duisburg-Essen, Germany; Institute of Neurology (G.S.), Catholic University of Sacred Heart; SPInal REhabilitation Lab (SPIRE) (M.M.), Fondazione Santa Lucia, IRCCS, Rome, Italy; Department of Neurology (T.K., C.N.), Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich; German Center for Neurodegenerative Diseases (DZNE) (T.K., C.N.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich; Department of Neurology (C.G.), University Medical Center Hamburg-Eppendorf (UKE), Germany; Department of Neuroscience and Reproductive and Odontostomatological Sciences (A.F.), Federico II University, Naples, Italy; Centogene AG (P.B.), Rostock, Germany; Pierre Louis Institute of Epidemiology and Public Health (S.T.d.M.), Pierre and Marie Curie University (UPMC); and AP-HP (S.T.d.M.), Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Sylvia Boesch
From the Department of Neurology (I.G., T.K.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G., H.J., B.P., T.K.), Bonn; Institute of Medical Genetics and Applied Genomics (F.H., M.S.) and Department of Neurodegenerative Diseases (L.S., M.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (H.J.), Heidelberg University Hospital; Department of Neurology (S.V.), Otto-von-Guericke University Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (S.V., J.M.), Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (L.S., M.S.), Tübingen, Germany; Department of Neurology (C.T., I.M.W.), Oslo University Hospital; Faculty of Medicine (C.T.), Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology (S.B., A.E.), Medical University Innsbruck, Austria; Department of Neurology (B.v.d.W., J.v.G.), Radboud University Medical Center, Nijmegen, Netherlands; Department of Neurology (C.K., A.D.), University of Rostock; German Center for Neurodegenerative Diseases (DZNE) (C.K., A.D.), Rostock; Department of Neurology (J.-S.K.), University of Frankfurt; Department of Neurology (D.T.), Essen University Hospital, University of Duisburg-Essen, Germany; Institute of Neurology (G.S.), Catholic University of Sacred Heart; SPInal REhabilitation Lab (SPIRE) (M.M.), Fondazione Santa Lucia, IRCCS, Rome, Italy; Department of Neurology (T.K., C.N.), Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich; German Center for Neurodegenerative Diseases (DZNE) (T.K., C.N.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich; Department of Neurology (C.G.), University Medical Center Hamburg-Eppendorf (UKE), Germany; Department of Neuroscience and Reproductive and Odontostomatological Sciences (A.F.), Federico II University, Naples, Italy; Centogene AG (P.B.), Rostock, Germany; Pierre Louis Institute of Epidemiology and Public Health (S.T.d.M.), Pierre and Marie Curie University (UPMC); and AP-HP (S.T.d.M.), Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Andreas Eigentler
From the Department of Neurology (I.G., T.K.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G., H.J., B.P., T.K.), Bonn; Institute of Medical Genetics and Applied Genomics (F.H., M.S.) and Department of Neurodegenerative Diseases (L.S., M.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (H.J.), Heidelberg University Hospital; Department of Neurology (S.V.), Otto-von-Guericke University Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (S.V., J.M.), Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (L.S., M.S.), Tübingen, Germany; Department of Neurology (C.T., I.M.W.), Oslo University Hospital; Faculty of Medicine (C.T.), Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology (S.B., A.E.), Medical University Innsbruck, Austria; Department of Neurology (B.v.d.W., J.v.G.), Radboud University Medical Center, Nijmegen, Netherlands; Department of Neurology (C.K., A.D.), University of Rostock; German Center for Neurodegenerative Diseases (DZNE) (C.K., A.D.), Rostock; Department of Neurology (J.-S.K.), University of Frankfurt; Department of Neurology (D.T.), Essen University Hospital, University of Duisburg-Essen, Germany; Institute of Neurology (G.S.), Catholic University of Sacred Heart; SPInal REhabilitation Lab (SPIRE) (M.M.), Fondazione Santa Lucia, IRCCS, Rome, Italy; Department of Neurology (T.K., C.N.), Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich; German Center for Neurodegenerative Diseases (DZNE) (T.K., C.N.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich; Department of Neurology (C.G.), University Medical Center Hamburg-Eppendorf (UKE), Germany; Department of Neuroscience and Reproductive and Odontostomatological Sciences (A.F.), Federico II University, Naples, Italy; Centogene AG (P.B.), Rostock, Germany; Pierre Louis Institute of Epidemiology and Public Health (S.T.d.M.), Pierre and Marie Curie University (UPMC); and AP-HP (S.T.d.M.), Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Bart van de Warrenburg
From the Department of Neurology (I.G., T.K.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G., H.J., B.P., T.K.), Bonn; Institute of Medical Genetics and Applied Genomics (F.H., M.S.) and Department of Neurodegenerative Diseases (L.S., M.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (H.J.), Heidelberg University Hospital; Department of Neurology (S.V.), Otto-von-Guericke University Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (S.V., J.M.), Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (L.S., M.S.), Tübingen, Germany; Department of Neurology (C.T., I.M.W.), Oslo University Hospital; Faculty of Medicine (C.T.), Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology (S.B., A.E.), Medical University Innsbruck, Austria; Department of Neurology (B.v.d.W., J.v.G.), Radboud University Medical Center, Nijmegen, Netherlands; Department of Neurology (C.K., A.D.), University of Rostock; German Center for Neurodegenerative Diseases (DZNE) (C.K., A.D.), Rostock; Department of Neurology (J.-S.K.), University of Frankfurt; Department of Neurology (D.T.), Essen University Hospital, University of Duisburg-Essen, Germany; Institute of Neurology (G.S.), Catholic University of Sacred Heart; SPInal REhabilitation Lab (SPIRE) (M.M.), Fondazione Santa Lucia, IRCCS, Rome, Italy; Department of Neurology (T.K., C.N.), Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich; German Center for Neurodegenerative Diseases (DZNE) (T.K., C.N.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich; Department of Neurology (C.G.), University Medical Center Hamburg-Eppendorf (UKE), Germany; Department of Neuroscience and Reproductive and Odontostomatological Sciences (A.F.), Federico II University, Naples, Italy; Centogene AG (P.B.), Rostock, Germany; Pierre Louis Institute of Epidemiology and Public Health (S.T.d.M.), Pierre and Marie Curie University (UPMC); and AP-HP (S.T.d.M.), Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Judith van Gaalen
From the Department of Neurology (I.G., T.K.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G., H.J., B.P., T.K.), Bonn; Institute of Medical Genetics and Applied Genomics (F.H., M.S.) and Department of Neurodegenerative Diseases (L.S., M.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (H.J.), Heidelberg University Hospital; Department of Neurology (S.V.), Otto-von-Guericke University Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (S.V., J.M.), Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (L.S., M.S.), Tübingen, Germany; Department of Neurology (C.T., I.M.W.), Oslo University Hospital; Faculty of Medicine (C.T.), Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology (S.B., A.E.), Medical University Innsbruck, Austria; Department of Neurology (B.v.d.W., J.v.G.), Radboud University Medical Center, Nijmegen, Netherlands; Department of Neurology (C.K., A.D.), University of Rostock; German Center for Neurodegenerative Diseases (DZNE) (C.K., A.D.), Rostock; Department of Neurology (J.-S.K.), University of Frankfurt; Department of Neurology (D.T.), Essen University Hospital, University of Duisburg-Essen, Germany; Institute of Neurology (G.S.), Catholic University of Sacred Heart; SPInal REhabilitation Lab (SPIRE) (M.M.), Fondazione Santa Lucia, IRCCS, Rome, Italy; Department of Neurology (T.K., C.N.), Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich; German Center for Neurodegenerative Diseases (DZNE) (T.K., C.N.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich; Department of Neurology (C.G.), University Medical Center Hamburg-Eppendorf (UKE), Germany; Department of Neuroscience and Reproductive and Odontostomatological Sciences (A.F.), Federico II University, Naples, Italy; Centogene AG (P.B.), Rostock, Germany; Pierre Louis Institute of Epidemiology and Public Health (S.T.d.M.), Pierre and Marie Curie University (UPMC); and AP-HP (S.T.d.M.), Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Christoph Kamm
From the Department of Neurology (I.G., T.K.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G., H.J., B.P., T.K.), Bonn; Institute of Medical Genetics and Applied Genomics (F.H., M.S.) and Department of Neurodegenerative Diseases (L.S., M.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (H.J.), Heidelberg University Hospital; Department of Neurology (S.V.), Otto-von-Guericke University Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (S.V., J.M.), Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (L.S., M.S.), Tübingen, Germany; Department of Neurology (C.T., I.M.W.), Oslo University Hospital; Faculty of Medicine (C.T.), Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology (S.B., A.E.), Medical University Innsbruck, Austria; Department of Neurology (B.v.d.W., J.v.G.), Radboud University Medical Center, Nijmegen, Netherlands; Department of Neurology (C.K., A.D.), University of Rostock; German Center for Neurodegenerative Diseases (DZNE) (C.K., A.D.), Rostock; Department of Neurology (J.-S.K.), University of Frankfurt; Department of Neurology (D.T.), Essen University Hospital, University of Duisburg-Essen, Germany; Institute of Neurology (G.S.), Catholic University of Sacred Heart; SPInal REhabilitation Lab (SPIRE) (M.M.), Fondazione Santa Lucia, IRCCS, Rome, Italy; Department of Neurology (T.K., C.N.), Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich; German Center for Neurodegenerative Diseases (DZNE) (T.K., C.N.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich; Department of Neurology (C.G.), University Medical Center Hamburg-Eppendorf (UKE), Germany; Department of Neuroscience and Reproductive and Odontostomatological Sciences (A.F.), Federico II University, Naples, Italy; Centogene AG (P.B.), Rostock, Germany; Pierre Louis Institute of Epidemiology and Public Health (S.T.d.M.), Pierre and Marie Curie University (UPMC); and AP-HP (S.T.d.M.), Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Ales Dudesek
From the Department of Neurology (I.G., T.K.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G., H.J., B.P., T.K.), Bonn; Institute of Medical Genetics and Applied Genomics (F.H., M.S.) and Department of Neurodegenerative Diseases (L.S., M.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (H.J.), Heidelberg University Hospital; Department of Neurology (S.V.), Otto-von-Guericke University Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (S.V., J.M.), Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (L.S., M.S.), Tübingen, Germany; Department of Neurology (C.T., I.M.W.), Oslo University Hospital; Faculty of Medicine (C.T.), Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology (S.B., A.E.), Medical University Innsbruck, Austria; Department of Neurology (B.v.d.W., J.v.G.), Radboud University Medical Center, Nijmegen, Netherlands; Department of Neurology (C.K., A.D.), University of Rostock; German Center for Neurodegenerative Diseases (DZNE) (C.K., A.D.), Rostock; Department of Neurology (J.-S.K.), University of Frankfurt; Department of Neurology (D.T.), Essen University Hospital, University of Duisburg-Essen, Germany; Institute of Neurology (G.S.), Catholic University of Sacred Heart; SPInal REhabilitation Lab (SPIRE) (M.M.), Fondazione Santa Lucia, IRCCS, Rome, Italy; Department of Neurology (T.K., C.N.), Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich; German Center for Neurodegenerative Diseases (DZNE) (T.K., C.N.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich; Department of Neurology (C.G.), University Medical Center Hamburg-Eppendorf (UKE), Germany; Department of Neuroscience and Reproductive and Odontostomatological Sciences (A.F.), Federico II University, Naples, Italy; Centogene AG (P.B.), Rostock, Germany; Pierre Louis Institute of Epidemiology and Public Health (S.T.d.M.), Pierre and Marie Curie University (UPMC); and AP-HP (S.T.d.M.), Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Jun-Suk Kang
From the Department of Neurology (I.G., T.K.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G., H.J., B.P., T.K.), Bonn; Institute of Medical Genetics and Applied Genomics (F.H., M.S.) and Department of Neurodegenerative Diseases (L.S., M.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (H.J.), Heidelberg University Hospital; Department of Neurology (S.V.), Otto-von-Guericke University Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (S.V., J.M.), Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (L.S., M.S.), Tübingen, Germany; Department of Neurology (C.T., I.M.W.), Oslo University Hospital; Faculty of Medicine (C.T.), Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology (S.B., A.E.), Medical University Innsbruck, Austria; Department of Neurology (B.v.d.W., J.v.G.), Radboud University Medical Center, Nijmegen, Netherlands; Department of Neurology (C.K., A.D.), University of Rostock; German Center for Neurodegenerative Diseases (DZNE) (C.K., A.D.), Rostock; Department of Neurology (J.-S.K.), University of Frankfurt; Department of Neurology (D.T.), Essen University Hospital, University of Duisburg-Essen, Germany; Institute of Neurology (G.S.), Catholic University of Sacred Heart; SPInal REhabilitation Lab (SPIRE) (M.M.), Fondazione Santa Lucia, IRCCS, Rome, Italy; Department of Neurology (T.K., C.N.), Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich; German Center for Neurodegenerative Diseases (DZNE) (T.K., C.N.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich; Department of Neurology (C.G.), University Medical Center Hamburg-Eppendorf (UKE), Germany; Department of Neuroscience and Reproductive and Odontostomatological Sciences (A.F.), Federico II University, Naples, Italy; Centogene AG (P.B.), Rostock, Germany; Pierre Louis Institute of Epidemiology and Public Health (S.T.d.M.), Pierre and Marie Curie University (UPMC); and AP-HP (S.T.d.M.), Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Dagmar Timmann
From the Department of Neurology (I.G., T.K.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G., H.J., B.P., T.K.), Bonn; Institute of Medical Genetics and Applied Genomics (F.H., M.S.) and Department of Neurodegenerative Diseases (L.S., M.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (H.J.), Heidelberg University Hospital; Department of Neurology (S.V.), Otto-von-Guericke University Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (S.V., J.M.), Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (L.S., M.S.), Tübingen, Germany; Department of Neurology (C.T., I.M.W.), Oslo University Hospital; Faculty of Medicine (C.T.), Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology (S.B., A.E.), Medical University Innsbruck, Austria; Department of Neurology (B.v.d.W., J.v.G.), Radboud University Medical Center, Nijmegen, Netherlands; Department of Neurology (C.K., A.D.), University of Rostock; German Center for Neurodegenerative Diseases (DZNE) (C.K., A.D.), Rostock; Department of Neurology (J.-S.K.), University of Frankfurt; Department of Neurology (D.T.), Essen University Hospital, University of Duisburg-Essen, Germany; Institute of Neurology (G.S.), Catholic University of Sacred Heart; SPInal REhabilitation Lab (SPIRE) (M.M.), Fondazione Santa Lucia, IRCCS, Rome, Italy; Department of Neurology (T.K., C.N.), Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich; German Center for Neurodegenerative Diseases (DZNE) (T.K., C.N.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich; Department of Neurology (C.G.), University Medical Center Hamburg-Eppendorf (UKE), Germany; Department of Neuroscience and Reproductive and Odontostomatological Sciences (A.F.), Federico II University, Naples, Italy; Centogene AG (P.B.), Rostock, Germany; Pierre Louis Institute of Epidemiology and Public Health (S.T.d.M.), Pierre and Marie Curie University (UPMC); and AP-HP (S.T.d.M.), Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Gabriella Silvestri
From the Department of Neurology (I.G., T.K.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G., H.J., B.P., T.K.), Bonn; Institute of Medical Genetics and Applied Genomics (F.H., M.S.) and Department of Neurodegenerative Diseases (L.S., M.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (H.J.), Heidelberg University Hospital; Department of Neurology (S.V.), Otto-von-Guericke University Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (S.V., J.M.), Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (L.S., M.S.), Tübingen, Germany; Department of Neurology (C.T., I.M.W.), Oslo University Hospital; Faculty of Medicine (C.T.), Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology (S.B., A.E.), Medical University Innsbruck, Austria; Department of Neurology (B.v.d.W., J.v.G.), Radboud University Medical Center, Nijmegen, Netherlands; Department of Neurology (C.K., A.D.), University of Rostock; German Center for Neurodegenerative Diseases (DZNE) (C.K., A.D.), Rostock; Department of Neurology (J.-S.K.), University of Frankfurt; Department of Neurology (D.T.), Essen University Hospital, University of Duisburg-Essen, Germany; Institute of Neurology (G.S.), Catholic University of Sacred Heart; SPInal REhabilitation Lab (SPIRE) (M.M.), Fondazione Santa Lucia, IRCCS, Rome, Italy; Department of Neurology (T.K., C.N.), Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich; German Center for Neurodegenerative Diseases (DZNE) (T.K., C.N.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich; Department of Neurology (C.G.), University Medical Center Hamburg-Eppendorf (UKE), Germany; Department of Neuroscience and Reproductive and Odontostomatological Sciences (A.F.), Federico II University, Naples, Italy; Centogene AG (P.B.), Rostock, Germany; Pierre Louis Institute of Epidemiology and Public Health (S.T.d.M.), Pierre and Marie Curie University (UPMC); and AP-HP (S.T.d.M.), Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Marcella Masciullo
From the Department of Neurology (I.G., T.K.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G., H.J., B.P., T.K.), Bonn; Institute of Medical Genetics and Applied Genomics (F.H., M.S.) and Department of Neurodegenerative Diseases (L.S., M.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (H.J.), Heidelberg University Hospital; Department of Neurology (S.V.), Otto-von-Guericke University Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (S.V., J.M.), Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (L.S., M.S.), Tübingen, Germany; Department of Neurology (C.T., I.M.W.), Oslo University Hospital; Faculty of Medicine (C.T.), Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology (S.B., A.E.), Medical University Innsbruck, Austria; Department of Neurology (B.v.d.W., J.v.G.), Radboud University Medical Center, Nijmegen, Netherlands; Department of Neurology (C.K., A.D.), University of Rostock; German Center for Neurodegenerative Diseases (DZNE) (C.K., A.D.), Rostock; Department of Neurology (J.-S.K.), University of Frankfurt; Department of Neurology (D.T.), Essen University Hospital, University of Duisburg-Essen, Germany; Institute of Neurology (G.S.), Catholic University of Sacred Heart; SPInal REhabilitation Lab (SPIRE) (M.M.), Fondazione Santa Lucia, IRCCS, Rome, Italy; Department of Neurology (T.K., C.N.), Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich; German Center for Neurodegenerative Diseases (DZNE) (T.K., C.N.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich; Department of Neurology (C.G.), University Medical Center Hamburg-Eppendorf (UKE), Germany; Department of Neuroscience and Reproductive and Odontostomatological Sciences (A.F.), Federico II University, Naples, Italy; Centogene AG (P.B.), Rostock, Germany; Pierre Louis Institute of Epidemiology and Public Health (S.T.d.M.), Pierre and Marie Curie University (UPMC); and AP-HP (S.T.d.M.), Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Thomas Klopstock
From the Department of Neurology (I.G., T.K.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G., H.J., B.P., T.K.), Bonn; Institute of Medical Genetics and Applied Genomics (F.H., M.S.) and Department of Neurodegenerative Diseases (L.S., M.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (H.J.), Heidelberg University Hospital; Department of Neurology (S.V.), Otto-von-Guericke University Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (S.V., J.M.), Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (L.S., M.S.), Tübingen, Germany; Department of Neurology (C.T., I.M.W.), Oslo University Hospital; Faculty of Medicine (C.T.), Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology (S.B., A.E.), Medical University Innsbruck, Austria; Department of Neurology (B.v.d.W., J.v.G.), Radboud University Medical Center, Nijmegen, Netherlands; Department of Neurology (C.K., A.D.), University of Rostock; German Center for Neurodegenerative Diseases (DZNE) (C.K., A.D.), Rostock; Department of Neurology (J.-S.K.), University of Frankfurt; Department of Neurology (D.T.), Essen University Hospital, University of Duisburg-Essen, Germany; Institute of Neurology (G.S.), Catholic University of Sacred Heart; SPInal REhabilitation Lab (SPIRE) (M.M.), Fondazione Santa Lucia, IRCCS, Rome, Italy; Department of Neurology (T.K., C.N.), Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich; German Center for Neurodegenerative Diseases (DZNE) (T.K., C.N.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich; Department of Neurology (C.G.), University Medical Center Hamburg-Eppendorf (UKE), Germany; Department of Neuroscience and Reproductive and Odontostomatological Sciences (A.F.), Federico II University, Naples, Italy; Centogene AG (P.B.), Rostock, Germany; Pierre Louis Institute of Epidemiology and Public Health (S.T.d.M.), Pierre and Marie Curie University (UPMC); and AP-HP (S.T.d.M.), Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Christiane Neuhofer
From the Department of Neurology (I.G., T.K.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G., H.J., B.P., T.K.), Bonn; Institute of Medical Genetics and Applied Genomics (F.H., M.S.) and Department of Neurodegenerative Diseases (L.S., M.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (H.J.), Heidelberg University Hospital; Department of Neurology (S.V.), Otto-von-Guericke University Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (S.V., J.M.), Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (L.S., M.S.), Tübingen, Germany; Department of Neurology (C.T., I.M.W.), Oslo University Hospital; Faculty of Medicine (C.T.), Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology (S.B., A.E.), Medical University Innsbruck, Austria; Department of Neurology (B.v.d.W., J.v.G.), Radboud University Medical Center, Nijmegen, Netherlands; Department of Neurology (C.K., A.D.), University of Rostock; German Center for Neurodegenerative Diseases (DZNE) (C.K., A.D.), Rostock; Department of Neurology (J.-S.K.), University of Frankfurt; Department of Neurology (D.T.), Essen University Hospital, University of Duisburg-Essen, Germany; Institute of Neurology (G.S.), Catholic University of Sacred Heart; SPInal REhabilitation Lab (SPIRE) (M.M.), Fondazione Santa Lucia, IRCCS, Rome, Italy; Department of Neurology (T.K., C.N.), Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich; German Center for Neurodegenerative Diseases (DZNE) (T.K., C.N.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich; Department of Neurology (C.G.), University Medical Center Hamburg-Eppendorf (UKE), Germany; Department of Neuroscience and Reproductive and Odontostomatological Sciences (A.F.), Federico II University, Naples, Italy; Centogene AG (P.B.), Rostock, Germany; Pierre Louis Institute of Epidemiology and Public Health (S.T.d.M.), Pierre and Marie Curie University (UPMC); and AP-HP (S.T.d.M.), Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Christos Ganos
From the Department of Neurology (I.G., T.K.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G., H.J., B.P., T.K.), Bonn; Institute of Medical Genetics and Applied Genomics (F.H., M.S.) and Department of Neurodegenerative Diseases (L.S., M.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (H.J.), Heidelberg University Hospital; Department of Neurology (S.V.), Otto-von-Guericke University Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (S.V., J.M.), Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (L.S., M.S.), Tübingen, Germany; Department of Neurology (C.T., I.M.W.), Oslo University Hospital; Faculty of Medicine (C.T.), Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology (S.B., A.E.), Medical University Innsbruck, Austria; Department of Neurology (B.v.d.W., J.v.G.), Radboud University Medical Center, Nijmegen, Netherlands; Department of Neurology (C.K., A.D.), University of Rostock; German Center for Neurodegenerative Diseases (DZNE) (C.K., A.D.), Rostock; Department of Neurology (J.-S.K.), University of Frankfurt; Department of Neurology (D.T.), Essen University Hospital, University of Duisburg-Essen, Germany; Institute of Neurology (G.S.), Catholic University of Sacred Heart; SPInal REhabilitation Lab (SPIRE) (M.M.), Fondazione Santa Lucia, IRCCS, Rome, Italy; Department of Neurology (T.K., C.N.), Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich; German Center for Neurodegenerative Diseases (DZNE) (T.K., C.N.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich; Department of Neurology (C.G.), University Medical Center Hamburg-Eppendorf (UKE), Germany; Department of Neuroscience and Reproductive and Odontostomatological Sciences (A.F.), Federico II University, Naples, Italy; Centogene AG (P.B.), Rostock, Germany; Pierre Louis Institute of Epidemiology and Public Health (S.T.d.M.), Pierre and Marie Curie University (UPMC); and AP-HP (S.T.d.M.), Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Alessandro Filla
From the Department of Neurology (I.G., T.K.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G., H.J., B.P., T.K.), Bonn; Institute of Medical Genetics and Applied Genomics (F.H., M.S.) and Department of Neurodegenerative Diseases (L.S., M.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (H.J.), Heidelberg University Hospital; Department of Neurology (S.V.), Otto-von-Guericke University Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (S.V., J.M.), Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (L.S., M.S.), Tübingen, Germany; Department of Neurology (C.T., I.M.W.), Oslo University Hospital; Faculty of Medicine (C.T.), Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology (S.B., A.E.), Medical University Innsbruck, Austria; Department of Neurology (B.v.d.W., J.v.G.), Radboud University Medical Center, Nijmegen, Netherlands; Department of Neurology (C.K., A.D.), University of Rostock; German Center for Neurodegenerative Diseases (DZNE) (C.K., A.D.), Rostock; Department of Neurology (J.-S.K.), University of Frankfurt; Department of Neurology (D.T.), Essen University Hospital, University of Duisburg-Essen, Germany; Institute of Neurology (G.S.), Catholic University of Sacred Heart; SPInal REhabilitation Lab (SPIRE) (M.M.), Fondazione Santa Lucia, IRCCS, Rome, Italy; Department of Neurology (T.K., C.N.), Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich; German Center for Neurodegenerative Diseases (DZNE) (T.K., C.N.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich; Department of Neurology (C.G.), University Medical Center Hamburg-Eppendorf (UKE), Germany; Department of Neuroscience and Reproductive and Odontostomatological Sciences (A.F.), Federico II University, Naples, Italy; Centogene AG (P.B.), Rostock, Germany; Pierre Louis Institute of Epidemiology and Public Health (S.T.d.M.), Pierre and Marie Curie University (UPMC); and AP-HP (S.T.d.M.), Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Peter Bauer
From the Department of Neurology (I.G., T.K.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G., H.J., B.P., T.K.), Bonn; Institute of Medical Genetics and Applied Genomics (F.H., M.S.) and Department of Neurodegenerative Diseases (L.S., M.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (H.J.), Heidelberg University Hospital; Department of Neurology (S.V.), Otto-von-Guericke University Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (S.V., J.M.), Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (L.S., M.S.), Tübingen, Germany; Department of Neurology (C.T., I.M.W.), Oslo University Hospital; Faculty of Medicine (C.T.), Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology (S.B., A.E.), Medical University Innsbruck, Austria; Department of Neurology (B.v.d.W., J.v.G.), Radboud University Medical Center, Nijmegen, Netherlands; Department of Neurology (C.K., A.D.), University of Rostock; German Center for Neurodegenerative Diseases (DZNE) (C.K., A.D.), Rostock; Department of Neurology (J.-S.K.), University of Frankfurt; Department of Neurology (D.T.), Essen University Hospital, University of Duisburg-Essen, Germany; Institute of Neurology (G.S.), Catholic University of Sacred Heart; SPInal REhabilitation Lab (SPIRE) (M.M.), Fondazione Santa Lucia, IRCCS, Rome, Italy; Department of Neurology (T.K., C.N.), Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich; German Center for Neurodegenerative Diseases (DZNE) (T.K., C.N.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich; Department of Neurology (C.G.), University Medical Center Hamburg-Eppendorf (UKE), Germany; Department of Neuroscience and Reproductive and Odontostomatological Sciences (A.F.), Federico II University, Naples, Italy; Centogene AG (P.B.), Rostock, Germany; Pierre Louis Institute of Epidemiology and Public Health (S.T.d.M.), Pierre and Marie Curie University (UPMC); and AP-HP (S.T.d.M.), Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Sophie Tezenas du Montcel
From the Department of Neurology (I.G., T.K.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G., H.J., B.P., T.K.), Bonn; Institute of Medical Genetics and Applied Genomics (F.H., M.S.) and Department of Neurodegenerative Diseases (L.S., M.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (H.J.), Heidelberg University Hospital; Department of Neurology (S.V.), Otto-von-Guericke University Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (S.V., J.M.), Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (L.S., M.S.), Tübingen, Germany; Department of Neurology (C.T., I.M.W.), Oslo University Hospital; Faculty of Medicine (C.T.), Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology (S.B., A.E.), Medical University Innsbruck, Austria; Department of Neurology (B.v.d.W., J.v.G.), Radboud University Medical Center, Nijmegen, Netherlands; Department of Neurology (C.K., A.D.), University of Rostock; German Center for Neurodegenerative Diseases (DZNE) (C.K., A.D.), Rostock; Department of Neurology (J.-S.K.), University of Frankfurt; Department of Neurology (D.T.), Essen University Hospital, University of Duisburg-Essen, Germany; Institute of Neurology (G.S.), Catholic University of Sacred Heart; SPInal REhabilitation Lab (SPIRE) (M.M.), Fondazione Santa Lucia, IRCCS, Rome, Italy; Department of Neurology (T.K., C.N.), Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich; German Center for Neurodegenerative Diseases (DZNE) (T.K., C.N.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich; Department of Neurology (C.G.), University Medical Center Hamburg-Eppendorf (UKE), Germany; Department of Neuroscience and Reproductive and Odontostomatological Sciences (A.F.), Federico II University, Naples, Italy; Centogene AG (P.B.), Rostock, Germany; Pierre Louis Institute of Epidemiology and Public Health (S.T.d.M.), Pierre and Marie Curie University (UPMC); and AP-HP (S.T.d.M.), Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Thomas Klockgether
From the Department of Neurology (I.G., T.K.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G., H.J., B.P., T.K.), Bonn; Institute of Medical Genetics and Applied Genomics (F.H., M.S.) and Department of Neurodegenerative Diseases (L.S., M.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (H.J.), Heidelberg University Hospital; Department of Neurology (S.V.), Otto-von-Guericke University Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (S.V., J.M.), Magdeburg; German Center for Neurodegenerative Diseases (DZNE) (L.S., M.S.), Tübingen, Germany; Department of Neurology (C.T., I.M.W.), Oslo University Hospital; Faculty of Medicine (C.T.), Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology (S.B., A.E.), Medical University Innsbruck, Austria; Department of Neurology (B.v.d.W., J.v.G.), Radboud University Medical Center, Nijmegen, Netherlands; Department of Neurology (C.K., A.D.), University of Rostock; German Center for Neurodegenerative Diseases (DZNE) (C.K., A.D.), Rostock; Department of Neurology (J.-S.K.), University of Frankfurt; Department of Neurology (D.T.), Essen University Hospital, University of Duisburg-Essen, Germany; Institute of Neurology (G.S.), Catholic University of Sacred Heart; SPInal REhabilitation Lab (SPIRE) (M.M.), Fondazione Santa Lucia, IRCCS, Rome, Italy; Department of Neurology (T.K., C.N.), Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich; German Center for Neurodegenerative Diseases (DZNE) (T.K., C.N.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich; Department of Neurology (C.G.), University Medical Center Hamburg-Eppendorf (UKE), Germany; Department of Neuroscience and Reproductive and Odontostomatological Sciences (A.F.), Federico II University, Naples, Italy; Centogene AG (P.B.), Rostock, Germany; Pierre Louis Institute of Epidemiology and Public Health (S.T.d.M.), Pierre and Marie Curie University (UPMC); and AP-HP (S.T.d.M.), Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Clinical and genetic characteristics of sporadic adult-onset degenerative ataxia
Ilaria Giordano, Florian Harmuth, Heike Jacobi, Brigitte Paap, Stefan Vielhaber, Judith Machts, Ludger Schöls, Matthis Synofzik, Marc Sturm, Chantal Tallaksen, Iselin M. Wedding, Sylvia Boesch, Andreas Eigentler, Bart van de Warrenburg, Judith van Gaalen, Christoph Kamm, Ales Dudesek, Jun-Suk Kang, Dagmar Timmann, Gabriella Silvestri, Marcella Masciullo, Thomas Klopstock, Christiane Neuhofer, Christos Ganos, Alessandro Filla, Peter Bauer, Sophie Tezenas du Montcel, Thomas Klockgether
Neurology Sep 2017, 89 (10) 1043-1049; DOI: 10.1212/WNL.0000000000004311
Citation Manager Formats
Make Comment
See Comments
Downloads
446
This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Abstract
Objective: To define the clinical phenotype and natural history of sporadic adult-onset degenerative ataxia and to identify putative disease-causing mutations.
Methods: The primary measure of disease severity was the Scale for the Assessment and Rating of Ataxia (SARA). DNA samples were screened for mutations using a high-coverage ataxia-specific gene panel in combination with next-generation sequencing.
Results: The analysis was performed on 249 participants. Among them, 83 met diagnostic criteria of clinically probable multiple system atrophy cerebellar type (MSA-C) at baseline and another 12 during follow-up. Positive MSA-C criteria (4.94 ± 0.74, p < 0.0001) and disease duration (0.22 ± 0.06 per additional year, p = 0.0007) were associated with a higher SARA score. Forty-eight participants who did not fulfill MSA-C criteria and had a disease duration of >10 years were designated sporadic adult-onset ataxia of unknown etiology/non-MSA (SAOA/non-MSA). Compared with MSA-C, SAOA/non-MSA patients had lower SARA scores (13.6 ± 6.0 vs 16.0 ± 5.8, p = 0.0200) and a slower annual SARA increase (1.1 ± 2.3 vs 3.3 ± 3.2, p = 0.0013). In 11 of 194 tested participants (6%), a definitive or probable genetic diagnosis was made.
Conclusions: Our study provides quantitative data on the clinical phenotype and progression of sporadic ataxia with adult onset. Screening for causative mutations with a gene panel approach yielded a genetic diagnosis in 6% of the cohort.
ClinicalTrials.gov registration: NCT02701036.
GLOSSARY
- INAS=
- Inventory of Non-Ataxia Signs;
- MSA=
- multiple system atrophy;
- MSA-C=
- multiple system atrophy cerebellar type;
- PHQ-9=
- Patient's Health Questionnaire;
- SAOA=
- sporadic adult-onset ataxia of unknown etiology;
- SARA=
- Scale for the Assessment and Rating of Ataxia;
- UMSARS=
- Unified MSA Rating Scale;
- VAS=
- visual analog scale;
- VUS=
- variant of uncertain clinical significance;
- WES=
- whole-exome sequencing
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at Neurology.org
- Received February 6, 2017.
- Accepted in final form June 12, 2017.
- © 2017 American Academy of Neurology
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
For assistance, please contact:
AAN Members (800) 879-1960 or (612) 928-6000 (International)
Non-AAN Member subscribers (800) 638-3030 or (301) 223-2300 option 3, select 1 (international)
Sign Up
Information on how to subscribe to Neurology and Neurology: Clinical Practice can be found here
Purchase
Individual access to articles is available through the Add to Cart option on the article page. Access for 1 day (from the computer you are currently using) is US$ 39.00. Pay-per-view content is for the use of the payee only, and content may not be further distributed by print or electronic means. The payee may view, download, and/or print the article for his/her personal, scholarly, research, and educational use. Distributing copies (electronic or otherwise) of the article is not allowed.
Letters: Rapid online correspondence
No comments have been published for this article.
REQUIREMENTS
You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
Advertisement
Topics Discussed
Alert Me
Recommended articles
-
Article
Molecular diagnosis of muscular diseases in outpatient clinicsA Canadian perspectiveFanny Thuriot, Elaine Gravel, Caroline Buote et al.Neurology: Genetics, March 13, 2020 -
Article
CDKL5 variantsImproving our understanding of a rare neurologic disorderRalph D. Hector, Vera M. Kalscheuer, Friederike Hennig et al.Neurology: Genetics, December 15, 2017 -
Articles
Evolution of sporadic olivopontocerebellar atrophy into multiple system atrophyS. Gilman, R. Little, J. Johanns et al.Neurology, August 22, 2000 -
Article
Natural History, Phenotypic Spectrum, and Discriminative Features of Multisystemic RFC1 DiseaseAndreas Traschütz, Andrea Cortese, Selina Reich et al.Neurology, January 25, 2021