Standardized Assessment of Hereditary Ataxia Patients in Clinical Studies

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. German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany; APHP Department of Genetics, Groupe Hospitalier Piti e-Salpêtri ere, Paris, France; Institut du Cerveau et de la Moelle, INSERM U1127, CNRS UMR7225, Sorbonne Universit es–UPMC Universit e Paris VI UMR_S1127, Paris, France; Department of Neurology and Hertie-Institute for Clinical Brain Research, University of T€ ubingen, T€ ubingen, Germany; German Center for Neurodegenerative Diseases (DZNE), T€ ubingen, Germany; Department of Neurology and Neuroscience Research Program, Methodist Hospital Research Institute, Houston, Texas, USA; Department of Neurology, Medical University Innsbruck, Innsbruck, Austria; School of Health Professions, Peninsula Allied Health Center, University of Plymouth, United Kingdom; Murdoch Children’s Research Institute, Melbourne, Australia; Clinical Genetics, Austin Health, Heidelberg, Victoria, Australia; Ataxia Centre Department of Molecularneuroscience, UCL Institute of Neurology, London, United Kingdom; Institut du Cerveau et de la Moelle (ICM) epiniere, Centre de NeuroImagerie de Recherche (CENIR), Paris, France; Service de Neuroradiologie, Groupe Hospitalier Pitie-Salpetriere, Paris, France; Unit of Genetics of Neurodegenerative and Metabolic Disorders, Fondazione IRCCS-Istituto Neurologico Carlo Besta, Milan, Italy; Department of Medical Genetics and Szentagothai Research Center, University of P ecs, P ecs, Hungary; Universit e Libre de Bruxelles, Brussels, Belgium; Department of Neurology, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, Oslo University, Oslo, Norway; Department of Neurology, Essen University Hospital, University of Duisburg-Essen, Essen, Germany; Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Neurology and JARA Brain, University Hospital, RWTH Aachen, Aachen, Germany; Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition, and Behavior, Nijmegen, The Netherlands; Department of Neurology, University Hospital of Bonn, Bonn, Germany *Correspondence to: Dr. Brigitte K. Paap, German Center for Neurodegenerative Diseases e.V. (DZNE), Clinical Research, Ernst-Robert-CurtiusStraße 12, D53117 Bonn, Germany; E-mail: [email protected]