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Updated: May 24, 2025
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
The association between white matter chronic inflammation and degeneration in multiple sclerosis: A combined
Silvia Tommasin1, Costanza Giannì2, Constantina A Treaba3
1Department of Human Neuroscienze, Sapienza University, Rome, Italy; UniCamillus - International Medical University in Rome, Italy.
Abstract:
In multiple sclerosis (MS), the interplay between white matter (WM) microglia mediated inflammation and degeneration is still unclear. Using positron emission tomography and diffusion tensor imaging, we assessed the association between WM chronic inflammation and damage in different regions including periventricular, deep, and subcortical WM and their association with clinical measures. Twenty-three people with MS (PwMS) and 13 healthy subjects underwent 11C-PBR28 imaging on an integrated 3T MR-Positron Emission Tomography system. PwMS showed a significantly higher normalized number of pathological voxels in normal appearing (NA) WM than in lesions (t = 5.51, p < 0.001), and this number was higher in subcortical than in periventricular (t = 5.49, p < 0.001) and deep NAWM (t = 4.94, p < 0.001). Number of pathological voxels in NAWM negatively correlated with fractional anisotropy (FA) in several areas. Expanded-Disability-Status-Scale correlated positively with number of pathological voxels within NAWM (r = 0.47, p < 0.02), while Symbol-Digit-Modalities-Test correlated positively with global NAWM FA (r = 0.57, p < 0.004) and negatively with lesion load (r=-0.55, p < 0.007). In the WM of PwMS, the higher the inflammation the higher the degeneration is, with both processes contributing to clinical measures. Inflammation and degeneration do not necessarily spatially overlap, and both follow a decreasing pattern from CSF, from periventricular surfaces for FA and cortical surfaces for inflammation.
Insights
In multiple sclerosis, white matter inflammation and degeneration are linked, with higher inflammation correlating with greater damage and impacting clinical measures. These processes occur in normal-appearing white matter, particularly in subcortical regions.
Area of Science:
- Neuroimaging
- Neuroinflammation
- White Matter Diseases
Background:
- The relationship between microglia-mediated inflammation and white matter (WM) degeneration in multiple sclerosis (MS) remains incompletely understood.
- Chronic inflammation and tissue damage in MS may not always occur in the same locations within the white matter.
Purpose of the Study:
- To investigate the association between chronic white matter inflammation and degeneration in different WM regions in people with MS (PwMS).
- To explore the relationship between these pathological processes and clinical outcomes in PwMS.
Main Methods:
- Utilized positron emission tomography (PET) with 11C-PBR28 and diffusion tensor imaging (DTI) on an integrated 3T MR-PET system.
- Assessed pathological voxels in normal-appearing (NA) WM and lesions, comparing inflammation levels across periventricular, deep, and subcortical WM regions.
- Correlated imaging findings with clinical measures like the Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT).
Main Results:
- PwMS exhibited significantly more pathological voxels in NAWM than in MS lesions.
- Inflammation was highest in subcortical NAWM compared to periventricular and deep NAWM.
- Increased inflammation in NAWM correlated negatively with fractional anisotropy (FA), indicating greater white matter damage.
- Higher EDSS scores correlated with increased inflammation in NAWM, while better SDMT performance correlated with higher global NAWM FA and lower lesion load.
Conclusions:
- In MS, white matter inflammation and degeneration are interconnected, with higher inflammation levels associated with increased tissue damage.
- Both inflammation and degeneration contribute to clinical disability in PwMS.
- These pathological processes do not necessarily overlap spatially and exhibit distinct distribution patterns within the white matter, decreasing from cerebrospinal fluid and cortical surfaces.
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