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Evolution of Clinical Outcome Measures and Biomarkers in Sporadic Adult-Onset Degenerative Ataxia.

Movement disorders : official journal of the Movement Disorder Society

Authors: Demet Oender, Jennifer Faber, Carlo Wilke, Tamara Schaprian, Asadeh Lakghomi, David Mengel, Ludger Schöls, Andreas Traschütz, Zofia Fleszar, Claudia Dufke, Stefan Vielhaber, Judith Machts, Ilaria Giordano, Marcus Grobe-Einsler, Thomas Klopstock, Claudia Stendel, Sylvia Boesch, Wolfgang Nachbauer, Dagmar Timmann-Braun, Andreas Gustafsson Thieme, Christoph Kamm, Ales Dudesek, Chantal Tallaksen, Iselin Wedding, Alessandro Filla, Matthias Schmid, Matthis Synofzik, Thomas Klockgether

BACKGROUND: Sporadic adult-onset ataxias without known genetic or acquired cause are subdivided into multiple system atrophy of cerebellar type (MSA-C) and sporadic adult-onset ataxia of unknown etiology (SAOA).

OBJECTIVES: To study the differential evolution of both conditions including plasma neurofilament light chain (NfL) levels and magnetic resonance imaging (MRI) markers.

METHODS: SPORTAX is a prospective registry of sporadic ataxia patients with an onset >40 years. Scale for the Assessment and Rating of Ataxia was the primary outcome measure. In subgroups, blood samples were taken and MRIs performed. Plasma NfL was measured via a single molecule assay. Regional brain volumes were automatically measured. To assess signal changes, we defined the pons and middle cerebellar peduncle abnormality score (PMAS). Using mixed-effects models, we analyzed changes on a time scale starting with ataxia onset.

RESULTS: Of 404 patients without genetic diagnosis, 130 met criteria of probable MSA-C at baseline and 26 during follow-up suggesting clinical conversion to MSA-C. The remaining 248 were classified as SAOA. At baseline, NfL, cerebellar white matter (CWM) and pons volume, and PMAS separated MSA-C from SAOA. NfL decreased in MSA-C and did not change in SAOA. CWM and pons volume decreased faster, whereas PMAS increased faster in MSA-C. In MSA-C, pons volume had highest sensitivity to change, and PMAS was a predictor of faster progression. Fulfillment of possible MSA criteria, NfL and PMAS were risk factors, CWM and pons volume protective factors for conversion to MSA-C.

CONCLUSIONS: This study provides detailed information on differential evolution and prognostic relevance of biomarkers in MSA-C and SAOA. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

PMID: 36695111

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