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Updated: Jan 31, 2026

Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
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Determinants of Deep Gray Matter Atrophy in Multiple Sclerosis: A Multimodal MRI Study

G Pontillo1,2, S Cocozza3, R Lanzillo4

  • 1From the Departments of Advanced Biomedical Sciences (G.P., S.C., C.R., M.D.S., C.P., E.A.V., E.T., A.E., A.B.).

AJNR. American Journal of Neuroradiology
|December 22, 2018
PubMed
Abstract

Insights

Multiple sclerosis (MS) affects deep gray matter, causing atrophy. In relapsing-remitting MS, white matter lesions drive atrophy, while progressive MS atrophy is linked to microstructural damage and susceptibility changes.

Area of Science:

  • Neuroimaging
  • Neurology
  • Radiology

Background:

  • Deep gray matter (DGM) involvement is a consistent feature in multiple sclerosis (MS).
  • Understanding DGM alterations is crucial for characterizing MS phenotypes.
  • Subcortical atrophy is a significant consequence of MS pathology.

Purpose of the Study:

  • To evaluate the relationship between DGM alterations and subcortical atrophy in MS.
  • To investigate the distinct substrates of volume loss in different MS phenotypes.
  • To differentiate the pathological drivers of DGM atrophy between relapsing-remitting MS and progressive MS.

Main Methods:

  • Seventy-seven MS patients (52 relapsing-remitting, 25 progressive) and 41 controls underwent MR imaging.
  • Volumetric, Diffusion Tensor Imaging (DTI), Perfusion Weighted Imaging (PWI), and Quantitative Susceptibility Mapping (QSM) were performed.
  • Deep gray matter structures (thalamus, caudate, putamen, globus pallidus) were analyzed for volume and microstructural metrics.

Main Results:

  • MS patients exhibited significant atrophy across all deep gray matter structures (P < .001).
  • In relapsing-remitting MS, white matter (WM) lesion burden was the primary driver of DGM volume loss (P ≤ .006).
  • In progressive MS, local microstructural damage (P ≤ .01) and thalamic susceptibility changes (P = .05) were the main determinants of DGM atrophy.

Conclusions:

  • Deep gray matter is diffusely involved in MS, with phenotype-specific pathological substrates.
  • Subcortical gray matter atrophy in relapsing-remitting MS is mainly driven by global WM lesion burden.
  • In progressive MS, local microstructural damage and susceptibility changes are key factors in deep gray matter volume loss.

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