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A multimodal approach to assess the validity of atrophied T2-lesion volume as an MRI marker of disease progression in multiple sclerosis

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Abstract

Background

Atrophied T2-lesion volume (LV) is a novel MRI marker representing brain-lesion loss due to atrophy, able to predict long-term disability progression and conversion to secondary-progressive multiple sclerosis (MS).

Objective

To better characterize atrophied T2-LV via comparison with other multidisciplinary markers of MS progression.

Methods

We studied 127 MS patients (85 relapsing–remitting, RRMS and 42 progressive, PMS) and 20 clinically isolated syndrome (CIS) utilizing MRI, optical coherence tomography, and serum neurofilament light chain (sNfL) at baseline and at 5-year follow-up. Symbol Digit Modalities Test (SDMT) was obtained at follow-up. Atrophied T2-LV was calculated by combining baseline lesion masks with follow-up CSF partial-volume maps. Measures were compared between MS patients who developed or not disease progression (DP). Partial correlations between atrophied T2-LV and other biomarkers were performed, and corrected for multiple comparisons.

Results

Atrophied T2-LV was the only biomarker that significantly differentiated DP from non-DP patients over the follow-up (p = 0.007). In both DP and non-DP groups, atrophied T2-LV was associated with baseline T2-LV and T1-LV (both p = 0.003), absolute change of T1-LV (DP p = 0.038; non-DP p = 0.003) and percentage of brain volume change (both p = 0.003). Furthermore, in the DP group, atrophied T2-LV was related to baseline brain parenchymal (p = 0.017) and thalamic (p = 0.003) volumes, thalamic volume change and follow-up SDMT (both p = 0.003). In non-DP patients, atrophied T2-LV was significantly related to baseline sNfL (p = 0.008), contrast-enhancing LV (p = 0.02) and percentage ventricular volume change (p = 0.003).

Conclusion

Atrophied T2-LV is associated with disability accrual in MS, and to several multimodal markers of disease evolution.

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Funding

Funding was provided by Novartis Pharma AG, Basel, Switzerland and Swiss National Research Foundation (Grant number 320030_160221).

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Authors and Affiliations

  1. Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, 100 High Street, Buffalo, NY, 14203, USA

    Eleonora Tavazzi, Niels Bergsland, Dejan Jakimovski, Jesper Hagemeier, Michael G. Dwyer & Robert Zivadinov

  2. Departments of Medicine, Biomedicine and Clinical Research, Neurologic Clinic and Policlinic, University Hospital Basel, University of Basel, Basel, Switzerland

    Jens Kuhle & Aleksandra M. Maceski

  3. Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA

    Murali Ramanathan

  4. Novartis Pharma AG, Basel, Switzerland

    Davorka Tomic, Harald Kropshofer & David Leppert

  5. Center for Biomedical Imaging at Clinical Translational Science Institute, University at Buffalo, State University of New York, Buffalo, NY, USA

    Michael G. Dwyer & Robert Zivadinov

  6. Jacobs MS Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA

    Bianca Weinstock-Guttman & Ralph H. B. Benedict

Authors
  1. Eleonora Tavazzi
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  2. Niels Bergsland
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  6. Aleksandra M. Maceski
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  10. David Leppert
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  11. Michael G. Dwyer
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  12. Bianca Weinstock-Guttman
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  13. Ralph H. B. Benedict
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Corresponding author

Correspondence to Robert Zivadinov.

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Tavazzi, E., Bergsland, N., Kuhle, J. et al. A multimodal approach to assess the validity of atrophied T2-lesion volume as an MRI marker of disease progression in multiple sclerosis. J Neurol 267, 802–811 (2020). https://doi.org/10.1007/s00415-019-09643-z

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  • DOI: https://doi.org/10.1007/s00415-019-09643-z

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