Year: 2025
Type: article
Study design: Observational Study
Abstract: OBJECTIVE: The objective of this study was to characterize changes in candidate biomarkers in early multiple system atrophy (MSA) and identify baseline predictors of faster progression. METHODS: This 1-year, multicenter, prospective study assessed clinical, neuroimaging (3T-magnetic resonance imaging [MRI], dopamine transporter single-photon emission computed tomography [DaT-SPECT]), and neurofilament light chain (NfL) changes in patients with early MSA (< 5 years from symptom onset) and healthy controls (HCs). Clinical and biomarker changes from baseline to 6 months (M6) and 12 months (M12) were analyzed. Survival status was collected at 24 months. Mixed linear regression analyzed repeated measures, whereas univariate regression identified biomarkers linked to progression. Sample size simulations were conducted for future trials. RESULTS: Forty-one patients with MSA and 20 HCs were included in this study. The Unified Multiple System Atrophy Rating Scale (UMSARS)-I + II scores worsened (mean percent change from baseline was 19.8% at M6; 95% confidence interval [CI] = 13.3 to 26.4% and 31.1% 95% CI = 24.9 to 37.2% at M12). Patients with MSA showed increased cerebellar white matter and pons atrophy (M6 = -5.9 to -2.8% and M12 = -9 to -4.9%) and decreased striatal specific binding ratio (SBR; M6 = -15.8 to -7.9% and M12 = -24 to -10.4%). Patients with multiple system atrophy parkinsonian (MSA-P) exhibited greater striatal SBR reduction, whereas patients with multiple system atrophy cerebellar (MSA-C) had greater cerebellar and pons atrophy, evident at M6. Baseline brainstem and pons volume predicted clinical worsening at M6, whereas SBR predicted worsening at M12. Higher plasma NfL levels correlated with early dropout (14% at M12), worse UMSARS scores, lower SBR, and increased mortality risk within 24 months. INTERPRETATION: Neuroimaging changes occur within 6 months in early MSA. High plasma NfL levels are linked to increased mortality and dropout risk. Longitudinal biomarker assessments provide valuable insights into disease progression. ANN NEUROL 2026;99:96-113.
Source: Annals of Neurology
DOI: 10.1002/ana.70028
Authors: Margherita Fabbri, Natalia del Campo, Wassilios G. Meissner, Vanessa Rousseau, Agnès Sommet, Pierre Payoux, Pierre Gantet, Amel Drif, Hélène Catala, Claire Thalamas, Christine Tranchant, Franck Durif, Ana Marques, Alexandre Eusebio, Luc Defebvre, Jean‐Christophe Corvol, Stéphane Thobois, Anthime Flaus, Anne‐Gaelle Corbille, Solène Frismand, Beverley Patterson, Alexandra Foubert‐Samier, Anne Pavy‐Le Traon, Germain Arribarat, Patrice Péran, Olivier Rascol, the ASPIRE Study Group
Institutions: Université Toulouse III - Paul Sabatier, Inserm, Centre Hospitalier Universitaire de Toulouse, Centre d’Investigation Clinique 1436, Université de Toulouse, Toulouse NeuroImaging Center, Centre National de la Recherche Scientifique, Université de Bordeaux, Centre Hospitalier Universitaire de Bordeaux, Institut des Maladies Neurodégénératives, Hôpitaux Universitaires de Strasbourg, Hôpital d'Hautepierre, Centre Hospitalier Universitaire de Clermont-Ferrand, Université de Lille, Centre Hospitalier Universitaire de Lille, Sorbonne Université, Assistance Publique – Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Institut du Cerveau, Lyon 1 Université, Centre de Recherche en Neurosciences de Lyon, Hospices Civils de Lyon, Hôpital Pierre Wertheimer, Hôpital Louis Pradel, Centre d'Investigation Clinique de Nantes, Centre Hospitalier Régional et Universitaire de Nancy, King's College London, Ono Pharmaceutical (United Kingdom)
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,700
OpenAlex ID: W4413709297