Dynamics of pseudo‐atrophy in RRMS reveals predominant gray matter compartmentalization
Open Access
- 3 February 2021
- journal article
- research article
- Published by Wiley in Annals of Clinical and Translational Neurology
- Vol. 8 (3), 623-630
- https://doi.org/10.1002/acn3.51302
Abstract
Objective To assess the dynamics of “pseudo‐atrophy,” the accelerated brain volume loss observed after initiation of anti‐inflammatory therapies, in patients with multiple sclerosis (MS). Methods Monthly magnetic resonance imaging (MRI) data of patients from the IMPROVE clinical study (NCT00441103) comparing relapsing‐remitting MS patients treated with interferon beta‐1a (IFNβ‐1a) for 40 weeks versus those receiving placebo (16 weeks) and then IFNβ‐1a (24 weeks) were used to assess percentage of gray (PGMVC) and white matter (PWMVC) volume changes. Comparisons of PGMVC and PWMVC slopes were performed with a mixed effect linear model. In the IFNβ‐1a‐treated arm, a quadratic term was included in the model to evaluate the plateauing effect over 40 weeks. Results Up to week 16, PGMVC was −0.14% per month in the placebo and −0.27% per month in treated patients (P < 0.001). Over the same period, the decrease in PWMVC was −0.067% per month in the placebo and −0.116% per month in treated patients (P = 0.27). Similar changes were found in the group originally randomized to placebo when starting IFNβ‐1a treatment (week 16–40, reliability analysis). In the originally treated group, over 40 weeks, the decrease in PGMVC showed a significant (P < 0.001) quadratic component, indicating a plateauing at week 20. Interpretation Findings reported here add new insights into the complex mechanisms of pseudo‐atrophy and its relation to the compartmentalized inflammation occurring in the GM of MS patients. Ongoing and forthcoming clinical trials including MRI‐derived GM volume loss as an outcome measure need to account for potentially significant GM volume changes as part of the initial treatment effect.Keywords
This publication has 35 references indexed in Scilit:
- Jacobian integration method increases the statistical power to measure gray matter atrophy in multiple sclerosisNeuroImage: Clinical, 2014
- Efficacy and safety of subcutaneous interferon beta-1a in relapsing–remitting multiple sclerosis: Further outcomes from the IMPROVE studyJournal of the Neurological Sciences, 2012
- Effect of disease-modifying therapies on brain volume in relapsing–remitting multiple sclerosis: Results of a five-year brain MRI studyJournal of the Neurological Sciences, 2012
- Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosisBrain, 2011
- Evidence for acute neurotoxicity after chemotherapyAnnals of Neurology, 2010
- A Gradient of neuronal loss and meningeal inflammation in multiple sclerosisAnnals of Neurology, 2010
- Rapid benefits of a new formulation of subcutaneous interferon beta-1a in relapsing—remitting multiple sclerosisMultiple Sclerosis Journal, 2010
- Mechanisms of action of disease-modifying agents and brain volume changes in multiple sclerosisNeurology, 2008
- Enhanced brain extraction improves the accuracy of brain atrophy estimationNeuroImage, 2008
- Brain atrophy after immunoablation and stem cell transplantation in multiple sclerosisNeurology, 2006