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• W4367305066 abstract "<h3>Objective:</h3> To evaluate how natalizumab treatment impacts innate immune cell activation at chronic lesion edge. <h3>Background:</h3> 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. <h3>Design/Methods:</h3> 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. <h3>Results:</h3> 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. <h3>Conclusions:</h3> TSPO-PET-imaging enables longitudinal evaluation of smoldering inflammation associated with chronic MS lesions. One-year treatment with natalizumab reduced the inflammatory burden at the active rim of chronic MS lesions but did not impact the proportions of the chronic lesion subtypes. <b>Disclosure:</b> Ms. Nylund has received research support from Finnish MS Foundation. Ms. Nylund has received research support from Maire Taponen Foundation. Ms. Nylund has received research support from Finnish Cultural Foundation. Markus Matilainen has nothing to disclose. Dr. Sucksdorff has nothing to disclose. Mr. Polvinen has nothing to disclose. Dr. Airas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme. Dr. Airas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Airas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Airas has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche." @default.
• W4367305066 created "2023-04-29" @default.
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• W4367305066 date "2023-04-25" @default.
• W4367305066 modified "2023-09-26" @default.
• W4367305066 title "Impact of natalizumab on chronic active lesions (P11-3.011)" @default.
• W4367305066 doi "https://doi.org/10.1212/wnl.0000000000202981" @default.
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