High-Dose Pulse Glucocorticoid Treatment Prevents White Matter Spinal Cord Pseudoatrophy in Newly Diagnosed Multiple Sclerosis

Simone Sacco; Nico Papinutto; Vinicius A Schoeps; Shuiting Cheng; William A Stern; Haojun Zhao; Antje Bischof; Eduardo Caverzasi; Manula Dombagahawatta; Jeremy Juwono; Amit Akula; Christian Cordano; Alexandra Beaudry-Richard; Refujia Gomez; Meagan Harms; Adam Santaniello; Riley M Bove; Jeffrey M Gelfand; Douglas S Goodin; Ari J Green; Jorge R Oksenberg; Emmanuelle Waubant; Michael R Wilson; Scott S Zamvil; Bruce A C Cree; Stephen L Hauser; Roland G Henry

doi:10.1002/ana.27298

High-Dose Pulse Glucocorticoid Treatment Prevents White Matter Spinal Cord Pseudoatrophy in Newly Diagnosed Multiple Sclerosis

Ann Neurol. 2025 Jun 24. doi: 10.1002/ana.27298. Online ahead of print.

Authors

Simone Sacco¹, Nico Papinutto¹, Vinicius A Schoeps¹, Shuiting Cheng¹, William A Stern¹, Haojun Zhao¹, Antje Bischof², Eduardo Caverzasi^{3

4}, Manula Dombagahawatta¹, Jeremy Juwono¹, Amit Akula¹, Christian Cordano^{1

5

6}, Alexandra Beaudry-Richard⁷, Refujia Gomez¹, Meagan Harms¹, Adam Santaniello¹, Riley M Bove¹, Jeffrey M Gelfand¹, Douglas S Goodin¹, Ari J Green¹, Jorge R Oksenberg¹, Emmanuelle Waubant¹, Michael R Wilson¹, Scott S Zamvil¹, Bruce A C Cree¹, Stephen L Hauser¹, Roland G Henry¹

Affiliations

¹ Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA.
² Department of Neurology, University Hospital of Muenster, Muenster, Germany.
³ Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
⁴ Advanced Imaging and Artificial Intelligence, Department of Neuroradiology, IRCCS Mondino Foundation, Pavia, Italy.
⁵ Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy.
⁶ IRCCS Ospedale Policlinico San Martino, Genova, Italy.
⁷ Department of Microbiology and Immunology, University of Ottawa, Ottawa, Canada.

PMID: 40552528
DOI: 10.1002/ana.27298

Abstract

Objective: Spinal cord (SC) atrophy correlates with and predicts the underlying progressive biology in active and non-active multiple sclerosis (MS), thereby providing a biomarker for clinical trials and patient management. Initiation of disease-modifying therapy (DMT) may be followed by early pronounced central nervous system (CNS) volume loss due to resolution of inflammation (pseudoatrophy) and confounding the interpretation of atrophy. High-dose glucocorticoids (HDGs) reduce inflammation and might therefore modify pseudoatrophy.

Methods: One hundred twenty-three newly diagnosed and DMT-naïve MS participants (relapsing-remitting, 70% female participants, median age = 36 years, Expanded Disability Status Scale [EDSS] 2.0) were followed for up to 3 years. Forty-two participants received HDG before baseline magnetic resonance imaging (MRI; DMT-HDG; median = 52 days, interquartile range [IQR] = 37-71), whereas 60 did not (DMT/no-HDG). Twenty-one participants remained untreated (no-DMT), and 102 started DMT after baseline MRI. SC total cervical cord cross-sectional area (TCA), gray matter area (GMA), and white matter area (WMA) and regional brain volumes were analyzed using mixed effects models.

Results: The DMT-HDG, DMT/no-HDG, and no-DMT groups had similar demographic, clinical, and radiological features. Pronounced SC pseudoatrophy was observed based on more year 1 versus year 2 volume loss for DMT/no-HDG (-2.06% vs. 0.83%; P = 0.02) but not DMT-HDG (-0.51% vs. 0.66%; P = 0.8) and more year 1 volume loss for DMT/no-HDG compared to DMT-HDG (-2.06% vs. 0.51%; P = 0.02).

Interpretation: HDG preceding baseline MRI suppresses CNS white matter (WM) pseudoatrophy after DMT initiation, most conspicuously for the SC. Suppression of pseudoatrophy with HDG may improve the fidelity of clinical trials and enhance the feasibility for short-term trials with SC and brain MRI outcomes in active MS by pretreatment with HDG. ANN NEUROL 2025.

Abstract

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