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Relevance of early cervical cord volume loss in the disease evolution of clinically isolated syndrome and early multiple sclerosis: a 2-year follow-up study

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Abstract

Upper cervical cord area (UCCA) atrophy is a prognostic marker for clinical progression in longstanding multiple sclerosis (MS). The objectives of the study were to quantify UCCA atrophy and evaluate its impact in clinically isolated syndrome (CIS) and relapsing–remitting MS (RRMS); to compare converting CIS patients with stable CIS, and to study changes of UCCA and brain white matter (WM) and grey matter (GM) at 2-year follow-up. 110 therapy-naive patients including 53 CIS [6 ± 6 months after symptom onset (SO)] and 57 early RRMS (SO: 12 ± 9 months) underwent sagittal 3D-T1w brain MR (3T). Mean UCCA (C1–C3 level), WM and GM, disability status (EDSS), pyramidal and sensory functional scores, motoric fatigue were assessed at baseline (BL), 12 and 24 months. Volumes were compared with 34 age- and gender-matched healthy controls to assess atrophy. RRMS (78.1 ± 8.7 mm2, p = 0.011) and converting CIS (77.3 ± 8.0 mm2, p = 0.046) presented with baseline UCCA atrophy, when compared with controls (82.7 ± 5.2 mm2), but not stable CIS (82.6 ± 7.4 mm2, p = 0.998). Baseline WM was reduced in RRMS (509.3 ± 25.7 ml vs. controls: 528.4 ± 24.1 ml, p = 0.032). Baseline UCCA correlated negative with muscular weakness and fatigability in all patients and RRMS. EDSS exceeding 3 was associated with lower baseline UCCA. Longitudinal atrophy rates were higher in UCCA than in brain volumes. Early cervical cord atrophy in CIS and RRMS was confirmed and may represent a potential new risk marker for conversion from CIS to MS. Baseline atrophy and atrophy change rates were higher in UCCA compared to WM and GM, suggesting that cervical cord volumetry might become an additional MRI marker relevant in future clinical studies in CIS and early MS.

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Acknowledgements

This work was supported by the German Federal Ministry for Education and Research, BMBF, German Competence Network Multiple Sclerosis (KKNMS), Grant No. 01GI1307A and Grant No. 01GI0914.

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  1. Inga T. Hagström and Ruth Schneider contributed equally to the manuscript.

Authors and Affiliations

  1. Department of Diagnostic and Interventional Radiology and Nuclear Medicine, St. Josef Hospital, Ruhr-University Bochum, Gudrunstr. 56, 44791, Bochum, Germany

    Inga T. Hagström, Barbara Bellenberg, Odo Köster & Carsten Lukas

  2. Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, Gudrunstr. 56, 44791, Bochum, Germany

    Ruth Schneider, Anke Salmen & Ralf Gold

  3. Department of Neurology, Inselspital, Bern University Hospital, Freiburgstrasse, 3010, Bern, Switzerland

    Anke Salmen

  4. Fraunhofer-MeVis Institute, Am Fallturm 1, 28359, Bremen, Germany

    Florian Weiler

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  1. Inga T. Hagström
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Correspondence to Carsten Lukas.

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Ethical standards

The study was approved by the local ethics committee (Approval No. 3714-10) and was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. Written informed consent was obtained from all participants prior to inclusion in the study.

Conflicts of interest

BB and AS received funding by the German Federal Ministry for Education and Research, BMBF, German Competence Network Multiple Sclerosis (KKNMS), Grant No. 01GI1601I and Grant No. 01GI0914. CL received a research grant by the German Federal Ministry for Education and Research, BMBF, German Competence Network Multiple Sclerosis (KKNMS), Grant No. 01GI1601I, has received consulting and speaker’s honoraria from BiogenIdec, Bayer Schering, Novartis, Sanofi, Genzyme and TEVA, and has received research scientific grant support from Bayer Schering, TEVA and MerckSerono. He holds an endowed professorship supported by the Novartis Foundation. RG received a research grant by the German Federal Ministry for Education and Research, BMBF, German Competence Network Multiple Sclerosis (KKNMS), Grant No. 01GI0914, has received honoraria, consultant fees or other support from Baxter, Bayer Schering, Biogen Idec, CLB, Behring, Genzyme, Merck Serono, Novartis, Talecris, Teva and Wyeth. All other authors declare that they have no conflict of interest in relation to the material presented in this manuscript.

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Hagström, I.T., Schneider, R., Bellenberg, B. et al. Relevance of early cervical cord volume loss in the disease evolution of clinically isolated syndrome and early multiple sclerosis: a 2-year follow-up study. J Neurol 264, 1402–1412 (2017). https://doi.org/10.1007/s00415-017-8537-5

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