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

Oender, Demet; Faber, Jennifer; Wilke, Carlo; Schaprian, Tamara; Lakghomi, Asadeh; Mengel, David; Schoels, Ludger; Traschuetz, Andreas; Fleszar, Zofia; Dufke, Claudia; Vielhaber, Stefan; Machts, Judith; Giordano, Ilaria; Grobe-Einsler, Marcus; Klopstock, Thomas; Stendel, Claudia; Boesch, Sylvia; Nachbauer, Wolfgang; Timmann-Braun, Dagmar; Thieme, Andreas Gustafsson; Kamm, Christoph; Dudesek, Ales; Tallaksen, Chantal; Wedding, Iselin; Filla, Alessandro; Schmid, Matthias; Synofzik, Matthis und Klockgether, Thomas (2023): Evolution of Clinical Outcome Measures and Biomarkers in Sporadic Adult-Onset Degenerative Ataxia. In: Movement Disorders, Bd. 38, Nr. 4: S. 654-664

Abstract

BackgroundSporadic 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). ObjectivesTo study the differential evolution of both conditions including plasma neurofilament light chain (NfL) levels and magnetic resonance imaging (MRI) markers. MethodsSPORTAX 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. ResultsOf 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. ConclusionsThis study provides detailed information on differential evolution and prognostic relevance of biomarkers in MSA-C and SAOA. (c) 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198