Exploring the Transformation of Diffusely Abnormal White Matter Regions into Focal White Matter Lesions in SPMS

 

A new study published in the Multiple Sclerosis Journal indicates that diffusely abnormal white matter (DAWM) regions in the brain appear to evolve into focal white matter lesions (FWML) over time among patients with secondary progressive multiple sclerosis (SPMS)–an evolution that may be associated with clinical progression of SPMS.

According to the authors of the study, assessment of DAWM in progressive multiple sclerosis (MS) may serve as “a useful measure for therapies aiming to protect this at-risk tissue with the potential to slow progression.”

The researchers arrived at this conclusion after evaluating 589 participants with SPMS. Follow-up lasted 3 years (3951 time points). The researchers automatically segmented FWML and DAWM, and determined screening DAWM volumes that had evolved into FWML by the final visit, as well as normalized T1-weighted intensities indicative of damage severity in those voxels.

Important findings from the study included:

  • As disease duration increased, FWML volume increased and DAWM volume decreased.
  • Decreases in greater normalized T1-weighted intensity over time were observed in DAWM-to-FWML voxels, which is indicative of relatively greater tissue damage.
  • A positive association of the Expanded Disability Status Scale (EDSS) with FWML volumes (but not DAWM) was observed.
  • DAWM-to-FWML volume was found to be higher among patients with disease progression (2.75 cm3 vs 1.70 cm3).
  • A negative association of normalized T1-weighted intensity with DAWM-to-FWML was observed.


Neurology Learning Network discussed these findings and their clinical implications further with study author Mahsa Dadar, PhD, postdoctoral researcher at Laval University in Quebec, Canada.

Neurology Learning Network: What does your study add to the literature in terms of the role of DAWM regions in SPMS?

Dr Dadar: Previous studies have shown histopathological differences between DAWM and focal lesions, and have suggested a potential contribution of DAWM to progression and neurodegeneration in MS.

Our study has evaluated not only how DAWM volumes change over time, but also the transformation of one lesion type into another, namely DAWM turning into FWML. This analysis clearly shows the contribution of changes from DAWM-to-FWML to clinically confirmed progression.

NLN: How might these findings aid physicians in selecting therapies for the treatment of SPMS in the future, and could these findings inform future treatment guidelines for SPMS?

Dr Dadar: At this point of our project, we are only able to assess changes in DAWM at a group level, not on a per-subject basis. So, the assessment of changes in DAWM would be beneficial as an outcome measurement in the context of clinical trials developing drugs that could have an impact on progression. Our future work will focus on the use of such measures on a per-subject basis. Our method just requires 2 standard sequences (t1-weighted and t1-weighted), readily available in most studies following patients with magnetic resonance imaging.

NLN: What key clinical takeaways do you hope to leave with neurologists on this topic?

Dr Dadar: DAWM actively changes into FWML in SPMS, and it is this conversion towards a more severe type of damage that is associated with progression, grey matter atrophy, and specific EDSS sub-scores.

NLN: What is the next step in terms of future research in this area?

Dr Dadar: This project has assessed DAWM in a population of well-established patients with SPMS (mean duration 6 years). As of yet, we have not compared the longitudinal evolution of DAWM in relapsing-remitting MS and primary progressive MS patients, or the evolution of DAWM from the relapsing-remitting phase to the secondary progressive phase. This analysis is yet another avenue that our future work will take.

—Christina Vogt

Reference:
Dadar M, Narayanan S, Arnold DL, Collins DL, Maranzano J. Conversion of diffusely abnormal white matter to focal lesions is linked to progression in secondary progressive multiple sclerosis [Published online March 23, 2020]. Multiple Sclerosis J. doi:10.1177/1352458520912172