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Normative Modelling of Brain Volume in Multiple Sclerosis.

Max Korbmacher, Ingrid Anne Lie, Kristin Wesnes

    Medrxiv : the Preprint Server for Health Sciences
    |September 26, 2025
    PubMed
    Summary

    Multiple sclerosis (MS) shows brain atrophy, particularly in the thalamus, which correlates with disability. These findings help in MS diagnosis and prognosis.

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    Area of Science:

    • Neuroimaging
    • Neurology
    • Biostatistics

    Background:

    • Brain atrophy is a key indicator in multiple sclerosis (MS).
    • Normative models are crucial for contextualizing brain atrophy in MS for clinical applications and predictions.
    • Establishing population-based reference models for brain volumes is essential for understanding individual deviations.

    Purpose of the Study:

    • To establish normative models of MRI-derived regional brain volumes from a large healthy control cohort.
    • To apply these models to individuals with MS to assess deviations from normative values.
    • To investigate the association of these deviations with clinical outcomes and their stability over time.

    Main Methods:

    • Developed reference models using a large healthy control (HC) dataset (N=63,115).
    • Applied models to 362 individuals with MS, calculating Z-values for regional brain volumes.
    • Utilized propensity-matched comparisons and linear models to assess deviations and their clinical correlations.

    Main Results:

    • Identified a stable brain morphometric phenotype in MS, with thalamic volumes consistently lower than reference values.
    • Individuals with MS exhibited more extreme deviations (|Z|>1.96) compared to HCs (4.51 vs. 1.67).
    • Baseline deviations, especially in the thalamus and hippocampi, predicted long-term disability (EDSS).

    Conclusions:

    • MS presents a heterogeneous brain phenotype with significant deviations from normative values, particularly in subcortical regions like the thalamus.
    • Brain volume deviations are linked to clinical disability (EDSS) in MS patients.
    • These normative models and findings can potentially aid in MS diagnosis and prognosis.