Brigitte K Paap1, Sandra Roeske1, Alexandra Durr2,3, Ludger Schöls4,5, Tetsuo Ashizawa6, Sylvia Boesch7, Lisa M Bunn8, Martin B Delatycki9,10, Paola Giunti11, Stéphane Lehéricy3,12,13, Caterina Mariotti14, Jörg Melegh15, Massimo Pandolfo16, Chantal M E Tallaksen17,18, Dagmar Timmann19, Shoji Tsuji20, Jörg Bela Schulz21, Bart P van de Warrenburg22, Thomas Klockgether1,23. 1. German Center for Neurodegenerative Diseases (DZNE) Bonn Germany. 2. APHP Department of Genetics Groupe Hospitalier Pitié-Salpêtrière Paris France. 3. Institut du Cerveau et de la Moelle INSERM U1127 CNRS UMR7225 Sorbonne Universités-UPMC Université Paris VI UMR_S1127 Paris France. 4. Department of Neurology and Hertie-Institute for Clinical Brain Research University of Tübingen Tübingen Germany. 5. German Center for Neurodegenerative Diseases (DZNE) Tübingen Germany. 6. Department of Neurology and Neuroscience Research Program Methodist Hospital Research Institute Houston Texas USA. 7. Department of Neurology Medical University Innsbruck Innsbruck Austria. 8. School of Health Professions Peninsula Allied Health Center University of Plymouth United Kingdom. 9. Murdoch Children's Research Institute Melbourne Australia. 10. Clinical Genetics Austin Health Heidelberg Victoria Australia. 11. Ataxia Centre Department of Molecularneuroscience UCL Institute of Neurology London United Kingdom. 12. Institut du Cerveau et de la Moelle (ICM) epiniere Centre de NeuroImagerie de Recherche (CENIR) Paris France. 13. Service de Neuroradiologie Groupe Hospitalier Pitie-Salpetriere Paris France. 14. Unit of Genetics of Neurodegenerative and Metabolic Disorders Fondazione IRCCS-Istituto Neurologico Carlo Besta Milan Italy. 15. Department of Medical Genetics and Szentagothai Research Center University of Pécs Pécs Hungary. 16. Université Libre de Bruxelles Brussels Belgium. 17. Department of Neurology Oslo University Hospital Oslo Norway. 18. Faculty of Medicine Oslo University Oslo Norway. 19. Department of Neurology Essen University Hospital University of Duisburg-Essen Essen Germany. 20. Department of Neurology Graduate School of Medicine The University of Tokyo Tokyo Japan. 21. Department of Neurology and JARA Brain University Hospital RWTH Aachen Aachen Germany. 22. Department of Neurology Radboud University Medical Center Donders Institute for Brain, Cognition, and Behavior Nijmegen The Netherlands. 23. Department of Neurology University Hospital of Bonn Bonn Germany.
Abstract
BACKGROUND: Hereditary ataxias are a heterogeneous group of degenerative diseases of the cerebellum, brainstem, and spinal cord. They may present with isolated ataxia or with additional symptoms going beyond cerebellar deficits. There are an increasing number of clinical studies with the goal to define the natural history of these disorders, develop biomarkers, and investigate therapeutic interventions. Especially, early and preclinical disease stages are currently of particular interest. METHODS AND RESULTS: Evidence-based, we review standards for sampling and storage of biomaterials, clinical and neuropsychological assessment, as well as neurophysiology and neuroimaging and recommendations for standardized assessment of ataxia patients in multicenter studies. CONCLUSIONS: DNA, RNA, serum, and, if possible, cerebrospinal fluid samples should be processed following established standards. Clinical assessment in ataxia studies must include use of a validated clinical ataxia scale. There are several validated clinical ataxia scales available. There are no instruments that were specifically designed for assessing neuropsychological and psychiatric symptoms in ataxia disorders. We provide a list of tests that may prove valuable. Quantitative performance tests have the potential to supplement clinical scales. They provide additional objective and quantitative information. Posturography and quantitative movement analysis-despite valid approaches-require standardization before implemented in multicenter studies. Standardization of neurophysiological tools, as required for multicenter interventional trials, is still lacking. Future multicenter neuroimaging studies in ataxias should implement quality assurance measures as defined by the ADNI or other consortia. MRI protocols should allow morphometric analyses.
BACKGROUND: Hereditary ataxias are a heterogeneous group of degenerative diseases of the cerebellum, brainstem, and spinal cord. They may present with isolated ataxia or with additional symptoms going beyond cerebellar deficits. There are an increasing number of clinical studies with the goal to define the natural history of these disorders, develop biomarkers, and investigate therapeutic interventions. Especially, early and preclinical disease stages are currently of particular interest. METHODS AND RESULTS: Evidence-based, we review standards for sampling and storage of biomaterials, clinical and neuropsychological assessment, as well as neurophysiology and neuroimaging and recommendations for standardized assessment of ataxia patients in multicenter studies. CONCLUSIONS: DNA, RNA, serum, and, if possible, cerebrospinal fluid samples should be processed following established standards. Clinical assessment in ataxia studies must include use of a validated clinical ataxia scale. There are several validated clinical ataxia scales available. There are no instruments that were specifically designed for assessing neuropsychological and psychiatric symptoms in ataxia disorders. We provide a list of tests that may prove valuable. Quantitative performance tests have the potential to supplement clinical scales. They provide additional objective and quantitative information. Posturography and quantitative movement analysis-despite valid approaches-require standardization before implemented in multicenter studies. Standardization of neurophysiological tools, as required for multicenter interventional trials, is still lacking. Future multicenter neuroimaging studies in ataxias should implement quality assurance measures as defined by the ADNI or other consortia. MRI protocols should allow morphometric analyses.
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