Related Experiment Video
Updated: Nov 18, 2025
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Dynamics of pseudo-atrophy in RRMS reveals predominant gray matter compartmentalization
Nicola De Stefano1, Antonio Giorgio1, Giordano Gentile1
1Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
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.
Insights
Anti-inflammatory therapy in multiple sclerosis (MS) patients accelerates brain volume loss, known as pseudo-atrophy. This gray matter volume loss plateaus around 20 weeks, suggesting a significant initial treatment effect in MS.
Area of Science:
- Neuroimaging
- Neurology
- Multiple Sclerosis Research
Background:
- Pseudo-atrophy, characterized by accelerated brain volume loss, is observed in multiple sclerosis (MS) patients initiating anti-inflammatory therapies.
- Understanding the dynamics of pseudo-atrophy is crucial for interpreting clinical trial outcomes and treatment effects in MS.
Purpose of the Study:
- To assess the dynamics of pseudo-atrophy in patients with relapsing-remitting multiple sclerosis (MS) treated with interferon beta-1a (IFNβ-1a).
- To evaluate the changes in gray matter (GM) and white matter (WM) volume during anti-inflammatory treatment in MS.
Main Methods:
- Utilized monthly magnetic resonance imaging (MRI) data from the IMPROVE clinical study (NCT00441103).
- Assessed percentage of gray matter volume change (PGMVC) and white matter volume change (PWMVC) in MS patients over 40 weeks.
- Employed mixed-effect linear models to compare PGMVC and PWMVC slopes between treatment and placebo groups, including a quadratic term to assess plateauing effects.
Main Results:
- Up to week 16, PGMVC was significantly higher in the IFNβ-1a treated group (-0.27%/month) compared to placebo (-0.14%/month).
- PWMVC changes were not significantly different between groups up to week 16.
- In the IFNβ-1a treated group, PGMVC showed a significant quadratic component, indicating a plateauing effect around week 20.
Conclusions:
- Pseudo-atrophy in MS patients involves accelerated gray matter volume loss, particularly in the initial phase of anti-inflammatory treatment.
- The observed plateauing of gray matter volume loss suggests a significant initial treatment effect that needs consideration in clinical trial outcome measures.
- Findings highlight the importance of accounting for GM volume changes as an early treatment effect in MS clinical trials using MRI outcomes.
