TSPO-Detectable Chronic Active Lesions Predict Disease Progression in Multiple Sclerosis

Abstract

<p><strong>Background and objectives: </strong>In the multiple sclerosis (MS) brain, chronic active lesions can be detected using MRI- and PET-based methods. In this study, we investigated whether the frequency of TSPO-PET-detectable chronic active lesions associates with disease progression measured using the Expanded Disability Status Scale (EDSS) at 5-year follow-up.</p><p><strong>Methods: </strong>Chronic lesion-associated innate immune cell activation was evaluated using TSPO-PET in 82 patients with MS. Chronic lesions were categorized into rim-active, inactive, and overall active lesion subtypes based on innate immune cell activation patterns in the lesion core and at the 2-mm perilesional rim. Logistic regression was used to identify best predictors of progression.</p><p><strong>Results: </strong>Twenty-one patients experienced disability progression during the follow-up. These patients had a significantly higher proportion of rim-active lesions (<em>p</em> < 0.001) and a significantly lower proportion of inactive lesions (<em>p</em> = 0.001) compared with nonprogressed patients. The results were similar in the patient group having no relapses during the follow-up (60 patients, 14 experienced progression). In logistic regression modeling, the categorized variable "patients with >10% rim-active lesions and ≤50% inactive lesions of all chronic lesions" predicted disease progression in the entire cohort (OR = 26.8, <em>p</em> < 0.001) and in the group free of relapses (OR = 34.8, <em>p</em> = 0.002).</p><p><strong>Discussion: </strong>The results show that single TSPO-PET-based in vivo lesion phenotyping of chronic MS lesions provides a strong predictor for MS disease progression. This emphasizes the significance of chronic active lesions in disability accumulation in MS.</p>