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. 2023 Sep 28;13:16279. doi: 10.1038/s41598-023-43618-5

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© The Author(s) 2023, corrected publication 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Panel A: Forest plot showing PBTL onset age minus clinical onset age (in years, x axis) for each of the 519 MS patients based on 1000 bootstrapping procedure. The center vertical red line represents the 0-reference line (clinical onset age). The tick marks in each horizontal line include the mean and 95% confidence interval. If the upper limit of 95% CI on the left of the center line, it suggests earlier onset. Otherwise, if the 95% CI includes the center line, it suggests simultaneous onset. Panels B and C: Bland–Altman plots. Each dot represents the difference between the age of onset of PBTL and the age of clinical onset. If the lower bound of 95% CI for the difference goes below the 0-reference line (red), it indicates weak evidence that the age of onset of progressive brain tissue loss is younger than the age of clinical onset. None of the dots are below the reference line in Panel B but they are in Panel C, consistent with our classification of “early” vs “simultaneous” onset. A High-resolution version of this Figure can be found in Supplementary Information 2.