Related Experiment Video
Updated: Jun 10, 2025
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Advanced MRI Measures of Myelin and Axon Volume Identify Repair in Multiple Sclerosis
Gretel Sanabria-Diaz1,2,3, Alessandro Cagol1,2,3,4, Po-Jui Lu1,2,3
1Neurology Clinic and Policlinic, Department of Medicine, Clinical Research and Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland.
Objective:
Pathological studies suggest that multiple sclerosis (MS) lesions endure multiple waves of damage and repair; however, the dynamics and characteristics of these processes are poorly understood in patients living with MS.
Methods:
We studied 128 MS patients (75 relapsing-remitting, 53 progressive) and 72 healthy controls who underwent advanced magnetic resonance imaging and clinical examination at baseline and 2 years later. Magnetization transfer saturation and multi-shell diffusion imaging were used to quantify longitudinal changes in myelin and axon volumes within MS lesions. Lesions were grouped into 4 classes (repair, damage, mixed repair damage, and stable). The frequency of each class was correlated to clinical measures, demographic characteristics, and levels of serum neurofilament light chain (sNfL).
Results:
Stable lesions were the most frequent (n = 2,276; 44%), followed by lesions with patterns of "repair" (n = 1,352; 26.2%) and damage (n = 1,214; 23.5%). The frequency of "repair" lesion was negatively associated with disability (β = -0.04; p < 0.001) and sNfL (β = -0.16; p < 0.001) at follow-up. The frequency of the "damage" class was higher in progressive than relapsing-remitting patients (p < 0.05) and was related to disability (baseline: β = -0.078; follow-up: β = -0.076; p < 0.001) and age (baseline: β = -0.078; p < 0.001). Stable lesions were more frequent in relapsing-remitting than in progressive patients (p < 0.05), and in younger patients versus older (β = -0.07; p < 0.001) at baseline. Further, "mixed" lesions were most frequent in older patients (β = 0.004; p < 0.001) at baseline.
Interpretation:
These findings show that repair and damage processes within MS lesions occur across the entire disease spectrum and that their frequency correlates with patients disability, age, disease duration, and extent of neuroaxonal damage. ANN NEUROL 2024.
Insights
Multiple sclerosis (MS) lesion repair is linked to less disability and lower neurofilament levels, while damage is more common in progressive MS and associated with disability and age. These processes vary across the disease spectrum.
Area of Science:
- Neuroimaging
- Neurology
- Pathology
Background:
- Multiple sclerosis (MS) pathology involves complex lesion dynamics of damage and repair.
- Understanding these longitudinal processes in MS patients is crucial but poorly characterized.
Purpose of the Study:
- To investigate the dynamics of lesion repair and damage in multiple sclerosis patients.
- To correlate lesion characteristics with clinical outcomes, demographics, and neuroaxonal damage markers.
Main Methods:
- Advanced MRI techniques (magnetization transfer saturation, multi-shell diffusion imaging) were used in 128 MS patients and 72 controls over 2 years.
- Lesions were classified into repair, damage, mixed, and stable categories.
- Frequencies of lesion classes were correlated with clinical disability, age, and serum neurofilament light chain (sNfL).
Main Results:
- Stable lesions were most frequent (44%), followed by repair (26.2%) and damage (23.5%) patterns.
- Higher frequency of 'repair' lesions correlated with lower disability and sNfL.
- The 'damage' class was more prevalent in progressive MS and associated with disability and age.
- Stable lesions were more common in relapsing-remitting and younger patients, while 'mixed' lesions were more frequent in older patients.
Conclusions:
- MS lesion repair and damage are dynamic processes occurring throughout the disease spectrum.
- The frequency of these lesion processes is significantly associated with patient disability, age, and neuroaxonal damage.
