학술논문
Genotype-specific spinal cord damage in spinocerebellar ataxias: an ENIGMA-Ataxia study.
Document Type
Academic Journal
Author
Rezende TJR; Department of Neurology, University of Campinas (UNICAMP), Campinas, Brazil thiago.jrezende@gmail.com.; Brazilian Institute of Neuroscience and Neurotechnology, Campinas, Brazil.; Adanyaguh I; Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, Minnesota, USA.; Barsottini OGP; Department of Neurology, Federal University of São Paulo, São Paulo, SP, Brazil.; Bender B; Department of Diagnostic and Interventional Neuroradiology, University Hospital Tübingen, Tübingen, Germany.; Cendes F; Department of Neurology, University of Campinas (UNICAMP), Campinas, Brazil.; Brazilian Institute of Neuroscience and Neurotechnology, Campinas, Brazil.; Coutinho L; Graduate program of Internal Medicine, Internal Medicine Department, Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil.; Deistung A; University Clinic and Outpatient Clinic for Radiology, Department for Radiation Medicine, University Hospital Halle (Saale), University Medicine Halle, Halle (Saale), Germany.; Dogan I; Department of Neurology, RWTH Aachen University, Aachen, Germany.; JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Research Center Jülich GmbH, Jülich, Germany.; Durr A; Sorbonne Université, Paris Brain Institute (ICM), Pitié-Salpêtrière Hospital, AP-HP, INSERM, CNRS, University Hospital Pitié-Salpêtrière, Paris, France.; Fernandez-Ruiz J; Neuropsychology Laboratory, Department of Physiology, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.; Göricke SL; Institute of Diagnostic and Interventional Radiology and Neuroradiology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Essen University Hospital, University of Duisburg-Essen, Essen, Germany.; Grisoli M; Department of Neuroradiology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.; Hernandez-Castillo CR; Faculty of Computer Science, Dalhousie University, Halifax, Nova Scotia, Canada.; Lenglet C; Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, Minnesota, USA.; Mariotti C; Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.; Martinez ARM; Department of Neurology, University of Campinas (UNICAMP), Campinas, Brazil.; Brazilian Institute of Neuroscience and Neurotechnology, Campinas, Brazil.; Massuyama BK; Department of Neurology, Federal University of São Paulo, São Paulo, SP, Brazil.; Mochel F; Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Paris, France.; Nanetti L; Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.; Nigri A; Department of Neuroradiology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.; Ono SE; Clínica DAPI - Diagnóstico Avançado Por Imagem, Curitiba, Brazil.; Öz G; Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, Minnesota, USA.; Pedroso JL; Department of Neurology, Federal University of São Paulo, São Paulo, SP, Brazil.; Reetz K; Department of Neurology, RWTH Aachen University, Aachen, Germany.; JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Research Center Jülich GmbH, Jülich, Germany.; Synofzik M; Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, Tübingen, Germany.; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.; Teive H; Graduate program of Internal Medicine, Internal Medicine Department, Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil.; Movement Disorders Unit, Neurology Service, Internal Medicine Department, Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil.; Thomopoulos SI; Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.; Thompson PM; Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.; Timmann D; Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Essen University Hospital, University of Duisburg-Essen, Essen, Germany.; van de Warrenburg BPC; Department of Neurology, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands.; Department of Neurology, Rijnstate Hospital, Arnhem, Netherlands.; van Gaalen J; Department of Neurology, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands.; Department of Neurology, Rijnstate Hospital, Arnhem, Netherlands.; França MC Jr; Department of Neurology, University of Campinas (UNICAMP), Campinas, Brazil.; Brazilian Institute of Neuroscience and Neurotechnology, Campinas, Brazil.; Harding IH; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.; Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.; Monash Biomedical Imaging, Monash University, Clayton, Victoria, Australia.
Source
Publisher: BMJ Publishing Group Country of Publication: England NLM ID: 2985191R Publication Model: Electronic Cited Medium: Internet ISSN: 1468-330X (Electronic) Linking ISSN: 00223050 NLM ISO Abbreviation: J Neurol Neurosurg Psychiatry Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Spinal cord damage is a feature of many spinocerebellar ataxias (SCAs), but well-powered in vivo studies are lacking and links with disease severity and progression remain unclear. Here we characterise cervical spinal cord morphometric abnormalities in SCA1, SCA2, SCA3 and SCA6 using a large multisite MRI dataset.
Methods: Upper spinal cord (vertebrae C1-C4) cross-sectional area (CSA) and eccentricity (flattening) were assessed using MRI data from nine sites within the ENIGMA-Ataxia consortium, including 364 people with ataxic SCA, 56 individuals with preataxic SCA and 394 nonataxic controls. Correlations and subgroup analyses within the SCA cohorts were undertaken based on disease duration and ataxia severity.
Results: Individuals in the ataxic stage of SCA1, SCA2 and SCA3, relative to non-ataxic controls, had significantly reduced CSA and increased eccentricity at all examined levels. CSA showed large effect sizes ( d >2.0) and correlated with ataxia severity (r<-0.43) and disease duration (r<-0.21). Eccentricity correlated only with ataxia severity in SCA2 (r=0.28). No significant spinal cord differences were evident in SCA6. In preataxic individuals, CSA was significantly reduced in SCA2 ( d =1.6) and SCA3 ( d =1.7), and the SCA2 group also showed increased eccentricity ( d =1.1) relative to nonataxic controls. Subgroup analyses confirmed that CSA and eccentricity are abnormal in early disease stages in SCA1, SCA2 and SCA3. CSA declined with disease progression in all, whereas eccentricity progressed only in SCA2.
Conclusions: Spinal cord abnormalities are an early and progressive feature of SCA1, SCA2 and SCA3, but not SCA6, which can be captured using quantitative MRI.
Competing Interests: Competing interests: TJRR, FC, ARMM, JLP, OB, BKM, IHH, AD, DT, SLG, ID, IA, GO, CM, LN, AN, MG, LC, HAGT, SEO, CRHR, JFR, FM, AD, BW, JG, MS, PMT, SIT: none. The authors declare no competing interests. KR received honoraria for presentations or advisory boards from Biogen and Roche as well as clinical trial grants from Pfizer, Merck, Minoryx, Biogen and Roche. BB is cofounder, shareholder and CTO of AIRAmed GmbH. CL received research grants from Minoryx Therapeutics and research support from Biogen Inc.
(© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)
Methods: Upper spinal cord (vertebrae C1-C4) cross-sectional area (CSA) and eccentricity (flattening) were assessed using MRI data from nine sites within the ENIGMA-Ataxia consortium, including 364 people with ataxic SCA, 56 individuals with preataxic SCA and 394 nonataxic controls. Correlations and subgroup analyses within the SCA cohorts were undertaken based on disease duration and ataxia severity.
Results: Individuals in the ataxic stage of SCA1, SCA2 and SCA3, relative to non-ataxic controls, had significantly reduced CSA and increased eccentricity at all examined levels. CSA showed large effect sizes ( d >2.0) and correlated with ataxia severity (r<-0.43) and disease duration (r<-0.21). Eccentricity correlated only with ataxia severity in SCA2 (r=0.28). No significant spinal cord differences were evident in SCA6. In preataxic individuals, CSA was significantly reduced in SCA2 ( d =1.6) and SCA3 ( d =1.7), and the SCA2 group also showed increased eccentricity ( d =1.1) relative to nonataxic controls. Subgroup analyses confirmed that CSA and eccentricity are abnormal in early disease stages in SCA1, SCA2 and SCA3. CSA declined with disease progression in all, whereas eccentricity progressed only in SCA2.
Conclusions: Spinal cord abnormalities are an early and progressive feature of SCA1, SCA2 and SCA3, but not SCA6, which can be captured using quantitative MRI.
Competing Interests: Competing interests: TJRR, FC, ARMM, JLP, OB, BKM, IHH, AD, DT, SLG, ID, IA, GO, CM, LN, AN, MG, LC, HAGT, SEO, CRHR, JFR, FM, AD, BW, JG, MS, PMT, SIT: none. The authors declare no competing interests. KR received honoraria for presentations or advisory boards from Biogen and Roche as well as clinical trial grants from Pfizer, Merck, Minoryx, Biogen and Roche. BB is cofounder, shareholder and CTO of AIRAmed GmbH. CL received research grants from Minoryx Therapeutics and research support from Biogen Inc.
(© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)