Objective:

To evaluate how natalizumab treatment impacts innate immune cell activation at chronic lesion edge.  

Background:

Increased innate immune cell activation has been associated with multiple sclerosis progression and neurodegeneration. We have demonstrated a reduction in microglial activation in the normal appearing white matter (NAWM) after natalizumab treatment. Later, a TSPO-PET-based method for phenotyping of chronic T1-lesions based on microglial activation in lesion core and at rim was developed. The impact of high-efficacy MS-treatments on microglial activation at the edge of chronic active lesions is not yet known.

Design/Methods:

10 MS-patients [age 49.15 (±9.33) years] underwent PET-imaging using ¹¹C-PK11195 radioligand and conventional MR-imaging before and after 1-year treatment with natalizumab. For comparison, 10 MS-patients [age 47.32 (±10.63)] with no disease modifying therapy were scanned similarly. T1-hypointense lesions were identified from MR-images at both time points and lesions were phenotyped based on the proportion of highly active PET-voxels at lesion rim and in lesion core. Disability assessment using Expanded Disability Status Scale was performed at time of imaging.

Results:

At baseline, natalizumab-treated patients had in total 24 rim-active (15% of all chronic lesions), 81 overall-active (50%) and 58 inactive (36%) lesions. The untreated cohort had 36 (15%) rim-active, 140 (57%) overall-active and 71 (29%) inactive lesions. The proportions of lesion types were unaltered during one-year follow-up in both groups, but the proportion of active voxels at the chronic active lesion rim was reduced more among natalizumab-treated patients compared to the untreated cohort [median change -7.7% (IQR -11.2– -4.5) vs. -0.5% (-2.4–0.7), p=0.015, Wilcoxon]. Similar changes were observed in the NAWM. 

Conclusions: