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Application of Quantitative Motor Assessments in Friedreich Ataxia and Evaluation of Their Relation to Clinical Measures

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Abstract

Friedreich’s ataxia (FRDA) is a rare autosomal-recessive slowly progressive neurodegenerative disorder. As common clinical measures for this devastating disease lack sensitivity, we explored whether (a) the quantitative motor assessments of the Q-Motor battery can enhance clinical characterisation of FRDA; (b) clinical measures can predict Q-Motor outcomes and (c) Q-Motor is sensitive to longitudinal change. At baseline 29 patients and 23 controls and in a 1-year follow-up 14 patients and 6 controls were included. The Q-Motor included lift (manumotography), finger tapping (digitomotography) and pronate/supinate (dysdiadochomotography) tasks. To model responses, a search of generalised linear models was conducted, selecting best fitting models, using demographic and clinical data as predictors. Predictors from selected models were used in linear mixed models to investigate longitudinal changes. Patients with FRDA performed worse than controls on most measures. Modelling of the pronate/supinate task was dominated by SCAFI (SCA functional index) subtasks, while tapping task and lift task models suggested a complex relationship with clinical measures. Longitudinal modelling implied minor changes from baseline to follow-up, while clinical scales mainly showed no change in this sample. Overall Q-Motor likely has favourable properties for assessing distinct motor aspects in severe FRDA as it can be administered in wheelchair-bound patients. Further longitudinal research is warranted to fully characterise its relation to routinely used measures and scales for FRDA.

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Funding

KR is funded by the German Federal Ministry of Education and Research (BMBF 01GQ1402). MS received support from the Else Kröner Fresenius Stiftung. ID was supported by the START-Program (08/16) of the Faculty of Medicine at the RWTH Aachen University.

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Authors and Affiliations

  1. Department of Neurology, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany

    Christian Hohenfeld, Imis Dogan, Claire Didszun, Jörg B. Schulz & Kathrin Reetz

  2. JARA-Brain Institute Molecular Neuroscience and Neuroimaging, Forschungszentrum Jülich GmbH/RWTH Aachen University, Aachen, Germany

    Christian Hohenfeld, Imis Dogan, Claire Didszun, Jörg B. Schulz & Kathrin Reetz

  3. George-Huntington-Institute, Technology-Park, Münster, Germany

    Robin Schubert & Ralf Reilmann

  4. Department of Neurodegenerative Diseases and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany

    Ludger Schöls, Matthis Synofzik & Ralf Reilmann

  5. German Centre for Neurodegenerative Diseases (DZNE), Tübingen, Germany

    Ludger Schöls & Matthis Synofzik

  6. Department of Neurology, University Hospital Bonn, Bonn, Germany

    Ilaria A. Giordano & Thomas Klockgether

  7. German Centre for Neurodegenerative Diseases (DZNE), Bonn, Germany

    Ilaria A. Giordano & Thomas Klockgether

  8. Department of Clinical Radiology, University of Münster, Münster, Germany

    Ralf Reilmann

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  1. Christian Hohenfeld
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  2. Imis Dogan
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  3. Robin Schubert
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  10. Ralf Reilmann
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  11. Kathrin Reetz
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Corresponding author

Correspondence to Kathrin Reetz.

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Conflict of Interest

R Schubert is employee of the George-Huntington-Institute and is involved in analysis and development of Q-Motor measures. He received funding from the EU-FP7 consortium REPAIR-HD to develop Q-Motor-based quantitative cognitive assessments.

T Klockgether receives/has received research support from the Deutsche Forschungsgemeinschaft (DFG), the Bundesministerium für Bildung und Forschung (BMBF), the Bundesministerium für Gesundheit (BMG), the Robert Bosch Foundation, the European Union (EU) and the National Institutes of Health (NIH). He has received consulting fees from Biohaven and UBC. He has received a speaker honorarium from Novartis.

R Reilmann is founding director and owner of the George-Huntington-Institute, a private research institute focused on clinical and preclinical research in Huntington disease, and QuantiMedis, a clinical research organisation providing Q-Motor (quantitative motor) services in clinical trials and research. He holds appointments at the Dept. of Radiology of the University of Muenster and at the Department of Neurodegenerative Diseases and Hertie-Institute for Clinical Brain Research, University of Tuebingen. Dr. Reilmann serves as elected member of the Steering Committees of the European Huntington Disease Network (EHDN) and the Huntington Study Group (HSG), co-chair of the Task Force on Huntington’s disease and member of the Task Force on Technology of the International Parkinson and Movement Disorder Society (IPMDS). He has provided consulting services, advisory board functions, clinical trial services, quantitative motor analyses and/or lectures for Actelion Pharmaceuticals, Amarin Neuroscience, AOP Orphan Pharmaceuticals, Cure Huntington Disease Initiative Foundation (CHDI), Desitin, Hoffmann-La Roche, IONIS Pharmaceuticals, Ipsen, Lundbeck, Link Medicine, MEDA Pharma, Medivation, Mitoconix, Neurosearch, Novartis AG, Omeros, Pfizer, Prana Biotechnology, Raptor Pharmaceuticals, Siena Biotech, Temmler Pharma, Teva Pharmaceuticals, uniQure, Vaccinex, Wave Life Sciences and Wyeth Pharmaceuticals. He has received grant support from the Bundesministerium für Bildung und Forschung (BMBF), the Cure Huntington Disease Initiative Foundation (CHDI), the Deutsche Forschungsgemeinschaft (DFG), the Deutsches Zentrum für Neurodegeneration und Entzündung (DZNE), the European Union 7th Framework Program (EU-FP7), the European Huntington Disease Network (EHDN), the High-Q-Foundation and the National Science Foundation (NSF).

All other authors declare that they have no conflict of interest.

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Ralf Reilmann and Kathrin Reetz shared last authorships

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Hohenfeld, C., Dogan, I., Schubert, R. et al. Application of Quantitative Motor Assessments in Friedreich Ataxia and Evaluation of Their Relation to Clinical Measures. Cerebellum 18, 896–909 (2019). https://doi.org/10.1007/s12311-019-01073-x

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