Magnetic Resonance Imaging Measures to Track Atrophy Progression in Progressive Supranuclear Palsy in Clinical Trials.
Magnetic Resonance Imaging Measures to Track Atrophy Progression in Progressive Supranuclear Palsy in Clinical Trials.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Munich, DE · Author affiliation
Department of Neurology, University Hospital, LMU Munich, Munich, Germany.Location evidence
Catanzaro, IT · Author affiliation
Institute of Neurology, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy.Location evidence
Gothenburg, SE · Author affiliation
University of Gothenburg, The Sahlgrenska Academy, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Mölndal and Gothenburg, Sweden.Location evidence
Mölndal, SE · Author affiliation
University of Gothenburg, The Sahlgrenska Academy, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Mölndal and Gothenburg, Sweden.Location evidence
Zürich, CH · Author affiliation
Swiss Epilepsy Clinic, Klinik Lengg, Zurich, Switzerland.Location evidence
Hannover, DE · Author affiliation
Department of Neurology, Hannover Medical School, Hannover, Germany.Location evidence
San Francisco, US · Author affiliation
Department of Neurology, University of California San Francisco, San Francisco, California, USA.Location evidence
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Original abstract
BackgroundSeveral magnetic resonance imaging (MRI) measures have been suggested as progression biomarkers in progressive supranuclear palsy (PSP), and some PSP staging systems have been recently proposed.ObjectiveComparing structural MRI measures and staging systems in tracking atrophy progression in PSP and estimating the sample size to use them as endpoints in clinical trials.MethodsProgressive supranuclear palsy-Richardson's syndrome (PSP-RS) patients with one-year-follow-up longitudinal brain MRI were selected from the placebo arms of international trials (NCT03068468, NCT01110720, NCT01049399) and the DescribePSP cohort. The discovery cohort included patients from the NCT03068468 trial; the validation cohort included patients from other sources. Multisite age-matched healthy controls (HC) were included for comparison. Several MRI measures were compared: automated atlas-based volumetry (44 regions), automated planimetric measures of brainstem regions, and four previously described staging systems, applied to volumetric data.ResultsOf 508 participants, 226 PSP patients including discovery (n = 121) and validation (n = 105) cohorts, and 251 HC were included. In PSP patients, the annualized percentage change of brainstem and midbrain volume, and a combined index including midbrain, frontal lobe, and third ventricle volume change, were the progression biomarkers with the highest effect size in both cohorts (discovery: >1.6; validation cohort: >1.3). These measures required the lowest sample sizes (n < 100) to detect 30% atrophy progression, compared with other volumetric/planimetric measures and staging systems.ConclusionsThis evidence may inform the selection of imaging endpoints to assess the treatment efficacy in reducing brain atrophy rate in PSP clinical trials, with automated atlas-based volumetry requiring smaller sample size than staging systems and planimetry to observe significant treatment effects. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.