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. 2023 Apr;38(4):654-664.
doi: 10.1002/mds.29324. Epub 2023 Jan 25.

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

Demet Oender  1   2 , Jennifer Faber  1   2 , Carlo Wilke  3 , Tamara Schaprian  1 , Asadeh Lakghomi  4 , David Mengel  3 , Ludger Schöls  3   5 , Andreas Traschütz  3   5 , Zofia Fleszar  3   5 , Claudia Dufke  6 , Stefan Vielhaber  7   8 , Judith Machts  7   8 , Ilaria Giordano  1   9 , Marcus Grobe-Einsler  1   2 , Thomas Klopstock  10   11   12 , Claudia Stendel  10   11 , Sylvia Boesch  13 , Wolfgang Nachbauer  13 , Dagmar Timmann-Braun  14 , Andreas Gustafsson Thieme  14 , Christoph Kamm  15   16 , Ales Dudesek  15   16 , Chantal Tallaksen  17 , Iselin Wedding  17 , Alessandro Filla  18 , Matthias Schmid  1   19 , Matthis Synofzik  3   5 , Thomas Klockgether  1   2
Affiliations

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

Demet Oender et al. Mov Disord. 2023 Apr.

Abstract

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.

Keywords: multiple system atrophy; natural history; neurofilament light chain; sporadic ataxia; volumetric MRI.

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