Sensitivity of Advanced Magnetic Resonance Imaging to Progression over Six Months in Early Spinocerebellar Ataxia-Reference-Cited by-同舟云学术

Sensitivity of Advanced Magnetic Resonance Imaging to Progression over Six Months in Early Spinocerebellar Ataxia

Published:2024-07-26 Issue: Volume: Page:
ISSN:0885-3185
Container-title:Movement Disorders
language:en
Short-container-title:Movement Disorders

Author:

Rezende Thiago J.R.¹^ORCID,Petit Emilien²^ORCID,Park Young Woo³,Tezenas du Montcel Sophie²,Joers James M.³,DuBois Jonathan M.⁴,Moore Arnold H.⁴,Povazan Michal⁵,Banan Guita⁶,Valabregue Romain²,Ehses Philipp⁷,Faber Jennifer⁷⁸,Coupé Pierrick⁹,Onyike Chiadi U.⁵,Barker Peter B.⁵,Schmahmann Jeremy D.¹⁰^ORCID,Ratai Eva‐Maria¹¹,Subramony Sub H.⁶,Mareci Thomas H.⁶,Bushara Khalaf O.³,Paulson Henry¹²,Klockgether Thomas⁷⁸^ORCID,Durr Alexandra²,Ashizawa Tetsuo¹³^ORCID,Lenglet Christophe³,Öz Gülin³^ORCID,

Affiliation:

1. Department of Neurology School of Medical Sciences, University of Campinas Campinas Brazil

2. Sorbonne Université, Paris Brain Institute, Inserm, INRIA, CNRS, APHP Paris France

3. Department of Radiology, Center for Magnetic Resonance Research, University of Minnesota Minneapolis Minnesota USA

4. Biogen Cambridge Massachusetts USA

5. Department of Radiology Johns Hopkins University, School of Medicine Baltimore Maryland USA

6. Norman Fixel Center for Neurological Disorders, College of Medicine, University of Florida Gainesville Florida USA

7. German Center for Neurodegenerative Diseases (DZNE) Bonn Germany

8. Department of Neurology University Hospital Bonn Bonn Germany

9. Laboratoire Bordelais de Recherche en Informatique, Université de Bordeaux Talence France

10. Laboratory for Neuroanatomy and Cerebellar Neurobiology, Department of Neurology, Ataxia Center Massachusetts General Hospital and Harvard Medical School Boston Massachusetts USA

11. A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Department of Radiology Harvard Medical School Boston Massachusetts USA

12. Department of Neurology University of Michigan Ann Arbor Michigan USA

13. Department of Neurology The Houston Methodist Research Institute Houston Texas USA

Abstract

AbstractBackgroundClinical trials for upcoming disease‐modifying therapies of spinocerebellar ataxias (SCA), a group of rare movement disorders, lack endpoints sensitive to early disease progression, when therapeutics will be most effective. In addition, regulatory agencies emphasize the importance of biological outcomes.ObjectivesREADISCA, a transatlantic clinical trial readiness consortium, investigated whether advanced multimodal magnetic resonance imaging (MRI) detects pathology progression over 6 months in preataxic and early ataxic carriers of SCA mutations.MethodsA total of 44 participants (10 SCA1, 25 SCA3, and 9 controls) prospectively underwent 3‐T MR scanning at baseline and a median [interquartile range] follow‐up of 6.2 [5.9–6.7] months; 44% of SCA participants were preataxic. Blinded analyses of annual changes in structural, diffusion MRI, MR spectroscopy, and the Scale for Assessment and Rating of Ataxia (SARA) were compared between groups using nonparametric testing. Sample sizes were estimated for 6‐month interventional trials with 50% to 100% treatment effect size, leveraging existing large cohort data (186 SCA1, 272 SCA3) for the SARA estimate.ResultsRate of change in microstructural integrity (decrease in fractional anisotropy, increase in diffusivities) in the middle cerebellar peduncle, corona radiata, and superior longitudinal fasciculus significantly differed in SCAs from controls (P < 0.005), with high effect sizes (Cohen's d = 1–2) and moderate‐to‐high responsiveness (|standardized response mean| = 0.6–0.9) in SCAs. SARA scores did not change, and their rate of change did not differ between groups.ConclusionsDiffusion MRI is sensitive to disease progression at very early‐stage SCA1 and SCA3 and may provide a >5‐fold reduction in sample sizes relative to SARA as endpoint for 6‐month‐long trials. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Funder

National Institute of Biomedical Imaging and Bioengineering

National Institute of Neurological Disorders and Stroke

National Institutes of Health

Publisher

Wiley

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