Lesion Repair, Damage Processes Correlate With MS Disease Characteristics

Advanced MRI shows multiple sclerosis (MS) lesions undergo repair and damage processes across the spectrum of the disease, according to a new study.

The authors of the study, published in the Annals of Neurology, also found that the frequency of these processes is associated with patients’ disability, age, disease duration, and the neuroaxonal damage.¹ The findings could allow clinicians to better understand patients’ disease progression, prognosis, and response to therapy.

Conventional MRI is an important tool in the diagnosis of MS as well as in long-term patient monitoring. However, corresponding author Gretel Sanabria-Diaz, PhD, of the University of Basel, Switzerland, and colleagues, said it lacks the specificity to be able to distinguish between degenerative and reparative processes inside and outside MS lesions.

The frequency of each lesion class—rather than the volume or number of lesions in each class—was related to clinical outcomes, demographics, and sNfL levels. | Image Credit: © New Africa - stock.adobe.com

Quantitative MRI (qMRI) makes it possible to perform biophysical measurements of tissue properties, Sanabria-Diaz and colleagues noted, and also provides details about factors such as the integrity of myelin, axon, and other central nervous tissue components.²

While numerous studies have looked at longitudinal changes of myelin and axon in white matter lesions (WML), the investigators said less attention has been devoted to assessing concomitant changes in myelin and axon using qMRI.

“As reparative processes are complex and involve simultaneous changes in various CNS tissue components, a combination of qMRI measures is probably more suitable for studying lesion repair,” they explained.

In the new study, Sanabria-Diaz and colleagues used qMRI to categorize WMLs based on the processes they were undergoing at the time: damage, repair, a mix of damage and repair, or stability. To do so, they used magnetization transfer saturation and multi-shell diffusion imaging.

“We then assessed the reparative and neurodegenerative phenomena within lesions by combining those parameters to obtain myelin volume fraction (MVF), and axon volume fraction (AVF),” they said.

They then analyzed whether the frequency of each class related to disease characteristics.

The investigators recruited 128 people with MS, most of whom (75) had relapsing-remitting disease; and the remainder of whom had progressive disease. Seventy-two healthy individuals were included as a control group. All participants underwent advanced MRI both at baseline and after 2 years.

The most common category of lesions was stable lesions (44%), but the investigators found 26.2% of lesions fit the parameters of the “repair” process, and 23.5% of lesions fit the definition of the “damage” phase. The frequency of lesion types was correlated with their disease status.

The frequency of “damage” lesions was higher in people with progressive disease than in those with relapsing-remitting disease (P < .05), and stable lesions were more frequent in people with relapsing-remitting disease (P < .05).

At baseline, the investigators found younger patients were more likely to have stable lesions (β = −0.07; P < .001), and older patients had the highest frequency of “mixed” lesions (β = −0.07; P < .001).

In addition, the investigators found the frequency of “repair” lesions was negatively associated with disability (β = −0.04; P < .001) and serum neurofilament light chain (sNfL) at follow-up (β = −0.16; P < .001).

Sanabria-Diaz and colleagues said it was “very interesting” that the frequency of each lesion class—rather than the volume or number of lesions in each class—was related to clinical outcomes, demographics, and sNfL levels.

“This finding points to the importance of considering the balance of all pathological processes occurring in [people with] MS to better understand and monitor this complex disorder,” they wrote.

The authors said future research should include longer and more numerous follow-ups in order to better understand lesion changes over time. They said the work might also be a useful tool in patient stratification and treatment evaluation.

References

1. Sanabria-Diaz G, Cagol A, Lu PJ, et al. Advanced MRI measures of myelin and axon volume identify repair in multiple sclerosis. Ann Neurol. Published online October 10, 2024. doi:10.1002/ana.27102
2. Granziera C, Wuerfel J, Barkhof F, et al. Quantitative magnetic resonance imaging towards clinical application in multiple sclerosis. Brain. 2021;144(5):1296-1311. doi:10.1093/brain/awab029