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Assessment of T2 lesion-based disease activity volume outcomes in predicting disease progression in multiple sclerosis over 10 years

  • Devon Oship
    Affiliations
    Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, 100 High St., Buffalo, NY 14203, United States
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  • Dejan Jakimovski
    Affiliations
    Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, 100 High St., Buffalo, NY 14203, United States
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  • Niels Bergsland
    Affiliations
    Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, 100 High St., Buffalo, NY 14203, United States

    IRCCS, Fondazione Don Carlo Gnocchi ONLUS, Milan, Italy
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  • Dana Horakova
    Affiliations
    Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
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  • Tomas Uher
    Affiliations
    Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
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  • Manuela Vaneckova
    Affiliations
    Department of Radiology, First Faculty of Medicine, Charles and General University Hospital in Prague, Prague, Czech Republic
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  • Eva Havrdova
    Affiliations
    Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
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  • Michael G. Dwyer
    Affiliations
    Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, 100 High St., Buffalo, NY 14203, United States

    Center for Biomedical Imaging at Clinical Translational Research Center, The State University of New York, Buffalo, NY, United States
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  • Robert Zivadinov
    Correspondence
    Corresponding author at: Buffalo Neuroimaging Analysis Center, Center Biomedical Imaging at Clinical Translational Research, Institute, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, 100 High St., Buffalo, NY 14203, United States.
    Affiliations
    Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, 100 High St., Buffalo, NY 14203, United States

    Center for Biomedical Imaging at Clinical Translational Research Center, The State University of New York, Buffalo, NY, United States
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Published:September 18, 2022DOI:https://doi.org/10.1016/j.msard.2022.104187

      Highlights

      • This study investigated the count vs. volume measures of lesion activity in 176 RR PwMS over a 10-year period.
      • PwMS with confirmed disability progression (CDP) had greater cumulative new/enlarging T2-LV compared to stable PwMS.
      • PwMS with CDP did not differ from stable ones in new/enlarging T2 lesion count or total T2-LV.
      • PwMS with EDSS change >2.0 had significantly greater enlarging T2 lesion count (p = 0.01) and enlarging T2-LV (p = 0.038).
      • Enlargement of T2 lesions is more strongly associated with long-term disability progression compared to other conventional T2 lesion-based outcomes.

      Abstract

      Background

      New/enlarging T2 lesion count and T2-lesion volume (LV) are used as conventional secondary endpoints in clinical trials of patients with multiple sclerosis (PwMS). However, those outcomes may have several limitations, such as inability to account for heterogeneity of lesion formation/enlargement frequency and their dynamic volumetric behavior. Measurement of volume rather than count of new/enlarging lesions may be more representative outcome of dynamic changes over time.

      Objectives

      To investigate whether new/enlarging T2-LV is more predictive of confirmed disability progression (CDP), compared to total T2-LV or new/enlarging T2 lesion count over long-term follow-up.

      Methods

      We studied 176 early relapsing-remitting PwMS who were followed with annual MRI examinations over 10 years. T2-LV, new/enlarging T2-LV, and new/enlarging lesion count were determined. Cumulative count/volumes were obtained. 10-year CDP was confirmed after 48-weeks. ANCOVA analysis detected MRI outcome differences in stable (n = 76) and CDP (n = 100) groups at different time points, after correction for multiple comparisons.

      Results

      PwMS with CDP had greater cumulative new/enlarging T2-LV at 4 years (p = 0.049), and enlarging T2-LV at 4- (p = 0.039) and 6-year follow-up (p = 0.032), compared to stable patients. PwMS with CDP did not differ from stable ones in new/enlarging T2 lesion count or total T2-LV at any of the study timepoints. PwMS with Expanded Disability Status Scale change >2.0 had significantly greater enlarging T2 lesion count (p = 0.01) and enlarging T2-LV (p = 0.038) over the 10-year follow-up.

      Conclusion

      Enlargement of T2 lesions is more strongly associated with long-term disability progression compared to other conventional T2 lesion-based outcomes.

      Keywords

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