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TSPO-Detectable Chronic Active Lesions Predict Disease Progression in Multiple Sclerosis
Eero Polvinen1, Markus Matilainen1, Marjo Nylund1
1From the Turku PET Centre (E.P., M.M., M.N., M.S., L.M.A.); Clinical Neurosciences (E.P., M.N., M.S., L.M.A.), University of Turku; Faculty of Science and Engineering (M.M.), Åbo Akademi University; and Neurocenter (M.S., L.M.A.), Turku University Hospital, Finland.
Background And Objectives:
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.
Methods:
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.
Results:
Twenty-one patients experienced disability progression during the follow-up. These patients had a significantly higher proportion of rim-active lesions (p < 0.001) and a significantly lower proportion of inactive lesions (p = 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, p < 0.001) and in the group free of relapses (OR = 34.8, p = 0.002).
Discussion:
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.
Insights
The frequency of chronic active lesions detected by TSPO-PET imaging predicts multiple sclerosis (MS) disease progression. Higher proportions of rim-active lesions indicate a greater risk of disability accumulation in MS patients.
Area of Science:
- Neuroimmunology
- Radiology
- Neurology
Background:
- Chronic active lesions in multiple sclerosis (MS) brain are detectable via MRI and PET imaging.
- Innate immune cell activation within these lesions is a key pathological feature.
Purpose of the Study:
- To investigate the association between TSPO-PET-detectable chronic active lesions and MS disease progression.
- To determine if lesion characteristics predict disability measured by the Expanded Disability Status Scale (EDSS) over a 5-year follow-up.
Main Methods:
- 82 MS patients underwent TSPO-PET imaging to assess chronic lesion activity.
- Lesions were classified as rim-active, inactive, or overall active based on immune cell patterns.
- Logistic regression analysis identified predictors of disease progression.
Main Results:
- Patients with disability progression showed a higher proportion of rim-active lesions and fewer inactive lesions.
- A specific lesion pattern ( >10% rim-active and ≤50% inactive lesions) strongly predicted progression (OR = 26.8).
- These findings held true even in patients without relapses during follow-up.
Conclusions:
- In vivo phenotyping of MS chronic lesions using TSPO-PET is a robust predictor of disease progression.
- The study highlights the critical role of chronic active lesions in MS disability accumulation.
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