Spontaneous remyelination in lesions protects the integrity of surrounding tissues over time in multiple sclerosis

Background and purpose: Lesion remyelination preserves axonal integrity in animal models of multiple sclerosis (MS), but an in vivo demonstration of its protective effect on surrounding tissues in humans is lacking.

Methods: Nineteen persons with MS were enrolled in a cohort study and underwent two positron emission tomography (PET)/magnetic resonance imaging (MRI) scans 1-4 months apart. Voxelwise maps of Pittsburgh compound B distribution volume ratio, reflecting myelin content, were used to calculate an index of baseline demyelination, and of dynamic demyelination and remyelination over the follow-up in 549 single white matter lesions. Changes in fractional anisotropy and mean diffusivity, reflecting microstructural damage, were calculated in the proximal and distal 3-mm-thick rings surrounding each lesion, and used to classify perilesional microstructure as "preserved" or "worsening" over the follow-up. Mixed-effect linear models and logistic regressions were employed to investigate whether PET-derived lesional indices were associated with changes in MRI metrics in perilesions, and to identify which of them best predicted the microstructural evolution of perilesions over time.

Results: A higher index of remyelination, and a lower index of baseline and dynamic demyelination in lesions were associated with a less severe microstructural deterioration of the corresponding proximal and distal perilesions over time (p-value range: <0.001-0.012), but the index of remyelination was the best predicting variable of perilesional fate. For every extra 1% of remyelination within each lesion, the probability of the corresponding perilesional microstructure remaining preserved over time increased by 39% (odds ratio = 6.62, 95% confidence interval = 2.16-20.32, p < 0.001).

Conclusions: Intralesional remyelination is associated with the microstructural preservation of surrounding tissues, possibly preventing neuroaxonal damage resulting from Wallerian degeneration.