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July 24, 2018; 91 (4) Article

Spinal cord volume loss

A marker of disease progression in multiple sclerosis

Charidimos Tsagkas, Stefano Magon, Laura Gaetano, Simon Pezold, Yvonne Naegelin, Michael Amann, Christoph Stippich, Philippe Cattin, Jens Wuerfel, Oliver Bieri, Till Sprenger, Ludwig Kappos, Katrin Parmar
First published June 27, 2018, DOI: https://doi.org/10.1212/WNL.0000000000005853
Charidimos Tsagkas
From the Department of Neurology (C.T., S.M., L.G., Y.N., M.A., T.S., L.K., K.P.), Division of Diagnostic and Interventional Neuroradiology, Department of Radiology (M.A., C.S.), and Division of Radiological Physics, Department of Radiology (O.B.), University Hospital Basel, University of Basel; Medical Image Analysis Center (MIAC AG) (C.T., S.M., L.G., M.A., J.W.), Basel; Department of Biomedical Engineering (S.P., P.C.), University of Basel, Switzerland; and Department of Neurology (T.S.), DKD HELIOS Klinik Wiesbaden, Germany.
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Stefano Magon
From the Department of Neurology (C.T., S.M., L.G., Y.N., M.A., T.S., L.K., K.P.), Division of Diagnostic and Interventional Neuroradiology, Department of Radiology (M.A., C.S.), and Division of Radiological Physics, Department of Radiology (O.B.), University Hospital Basel, University of Basel; Medical Image Analysis Center (MIAC AG) (C.T., S.M., L.G., M.A., J.W.), Basel; Department of Biomedical Engineering (S.P., P.C.), University of Basel, Switzerland; and Department of Neurology (T.S.), DKD HELIOS Klinik Wiesbaden, Germany.
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Laura Gaetano
From the Department of Neurology (C.T., S.M., L.G., Y.N., M.A., T.S., L.K., K.P.), Division of Diagnostic and Interventional Neuroradiology, Department of Radiology (M.A., C.S.), and Division of Radiological Physics, Department of Radiology (O.B.), University Hospital Basel, University of Basel; Medical Image Analysis Center (MIAC AG) (C.T., S.M., L.G., M.A., J.W.), Basel; Department of Biomedical Engineering (S.P., P.C.), University of Basel, Switzerland; and Department of Neurology (T.S.), DKD HELIOS Klinik Wiesbaden, Germany.
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Simon Pezold
From the Department of Neurology (C.T., S.M., L.G., Y.N., M.A., T.S., L.K., K.P.), Division of Diagnostic and Interventional Neuroradiology, Department of Radiology (M.A., C.S.), and Division of Radiological Physics, Department of Radiology (O.B.), University Hospital Basel, University of Basel; Medical Image Analysis Center (MIAC AG) (C.T., S.M., L.G., M.A., J.W.), Basel; Department of Biomedical Engineering (S.P., P.C.), University of Basel, Switzerland; and Department of Neurology (T.S.), DKD HELIOS Klinik Wiesbaden, Germany.
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Yvonne Naegelin
From the Department of Neurology (C.T., S.M., L.G., Y.N., M.A., T.S., L.K., K.P.), Division of Diagnostic and Interventional Neuroradiology, Department of Radiology (M.A., C.S.), and Division of Radiological Physics, Department of Radiology (O.B.), University Hospital Basel, University of Basel; Medical Image Analysis Center (MIAC AG) (C.T., S.M., L.G., M.A., J.W.), Basel; Department of Biomedical Engineering (S.P., P.C.), University of Basel, Switzerland; and Department of Neurology (T.S.), DKD HELIOS Klinik Wiesbaden, Germany.
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Michael Amann
From the Department of Neurology (C.T., S.M., L.G., Y.N., M.A., T.S., L.K., K.P.), Division of Diagnostic and Interventional Neuroradiology, Department of Radiology (M.A., C.S.), and Division of Radiological Physics, Department of Radiology (O.B.), University Hospital Basel, University of Basel; Medical Image Analysis Center (MIAC AG) (C.T., S.M., L.G., M.A., J.W.), Basel; Department of Biomedical Engineering (S.P., P.C.), University of Basel, Switzerland; and Department of Neurology (T.S.), DKD HELIOS Klinik Wiesbaden, Germany.
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Christoph Stippich
From the Department of Neurology (C.T., S.M., L.G., Y.N., M.A., T.S., L.K., K.P.), Division of Diagnostic and Interventional Neuroradiology, Department of Radiology (M.A., C.S.), and Division of Radiological Physics, Department of Radiology (O.B.), University Hospital Basel, University of Basel; Medical Image Analysis Center (MIAC AG) (C.T., S.M., L.G., M.A., J.W.), Basel; Department of Biomedical Engineering (S.P., P.C.), University of Basel, Switzerland; and Department of Neurology (T.S.), DKD HELIOS Klinik Wiesbaden, Germany.
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Philippe Cattin
From the Department of Neurology (C.T., S.M., L.G., Y.N., M.A., T.S., L.K., K.P.), Division of Diagnostic and Interventional Neuroradiology, Department of Radiology (M.A., C.S.), and Division of Radiological Physics, Department of Radiology (O.B.), University Hospital Basel, University of Basel; Medical Image Analysis Center (MIAC AG) (C.T., S.M., L.G., M.A., J.W.), Basel; Department of Biomedical Engineering (S.P., P.C.), University of Basel, Switzerland; and Department of Neurology (T.S.), DKD HELIOS Klinik Wiesbaden, Germany.
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Jens Wuerfel
From the Department of Neurology (C.T., S.M., L.G., Y.N., M.A., T.S., L.K., K.P.), Division of Diagnostic and Interventional Neuroradiology, Department of Radiology (M.A., C.S.), and Division of Radiological Physics, Department of Radiology (O.B.), University Hospital Basel, University of Basel; Medical Image Analysis Center (MIAC AG) (C.T., S.M., L.G., M.A., J.W.), Basel; Department of Biomedical Engineering (S.P., P.C.), University of Basel, Switzerland; and Department of Neurology (T.S.), DKD HELIOS Klinik Wiesbaden, Germany.
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Oliver Bieri
From the Department of Neurology (C.T., S.M., L.G., Y.N., M.A., T.S., L.K., K.P.), Division of Diagnostic and Interventional Neuroradiology, Department of Radiology (M.A., C.S.), and Division of Radiological Physics, Department of Radiology (O.B.), University Hospital Basel, University of Basel; Medical Image Analysis Center (MIAC AG) (C.T., S.M., L.G., M.A., J.W.), Basel; Department of Biomedical Engineering (S.P., P.C.), University of Basel, Switzerland; and Department of Neurology (T.S.), DKD HELIOS Klinik Wiesbaden, Germany.
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Till Sprenger
From the Department of Neurology (C.T., S.M., L.G., Y.N., M.A., T.S., L.K., K.P.), Division of Diagnostic and Interventional Neuroradiology, Department of Radiology (M.A., C.S.), and Division of Radiological Physics, Department of Radiology (O.B.), University Hospital Basel, University of Basel; Medical Image Analysis Center (MIAC AG) (C.T., S.M., L.G., M.A., J.W.), Basel; Department of Biomedical Engineering (S.P., P.C.), University of Basel, Switzerland; and Department of Neurology (T.S.), DKD HELIOS Klinik Wiesbaden, Germany.
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Ludwig Kappos
From the Department of Neurology (C.T., S.M., L.G., Y.N., M.A., T.S., L.K., K.P.), Division of Diagnostic and Interventional Neuroradiology, Department of Radiology (M.A., C.S.), and Division of Radiological Physics, Department of Radiology (O.B.), University Hospital Basel, University of Basel; Medical Image Analysis Center (MIAC AG) (C.T., S.M., L.G., M.A., J.W.), Basel; Department of Biomedical Engineering (S.P., P.C.), University of Basel, Switzerland; and Department of Neurology (T.S.), DKD HELIOS Klinik Wiesbaden, Germany.
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Katrin Parmar
From the Department of Neurology (C.T., S.M., L.G., Y.N., M.A., T.S., L.K., K.P.), Division of Diagnostic and Interventional Neuroradiology, Department of Radiology (M.A., C.S.), and Division of Radiological Physics, Department of Radiology (O.B.), University Hospital Basel, University of Basel; Medical Image Analysis Center (MIAC AG) (C.T., S.M., L.G., M.A., J.W.), Basel; Department of Biomedical Engineering (S.P., P.C.), University of Basel, Switzerland; and Department of Neurology (T.S.), DKD HELIOS Klinik Wiesbaden, Germany.
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Citation
Spinal cord volume loss
A marker of disease progression in multiple sclerosis
Charidimos Tsagkas, Stefano Magon, Laura Gaetano, Simon Pezold, Yvonne Naegelin, Michael Amann, Christoph Stippich, Philippe Cattin, Jens Wuerfel, Oliver Bieri, Till Sprenger, Ludwig Kappos, Katrin Parmar
Neurology Jul 2018, 91 (4) e349-e358; DOI: 10.1212/WNL.0000000000005853

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Abstract

Objective Cross-sectional studies have shown that spinal cord volume (SCV) loss is related to disease severity in multiple sclerosis (MS). However, long-term data are lacking. Our aim was to evaluate SCV loss as a biomarker of disease progression in comparison to other MRI measurements in a large cohort of patients with relapse-onset MS with 6-year follow-up.

Methods The upper cervical SCV, the total brain volume, and the brain T2 lesion volume were measured annually in 231 patients with MS (180 relapsing-remitting [RRMS] and 51 secondary progressive [SPMS]) over 6 years on 3-dimensional, T1-weighted, magnetization-prepared rapid-acquisition gradient echo images. Expanded Disability Status Scale (EDSS) score and relapses were recorded at every follow-up.

Results Patients with SPMS had lower baseline SCV (p < 0.01) but no accelerated SCV loss compared to those with RRMS. Clinical relapses were found to predict SCV loss over time (p < 0.05) in RRMS. Furthermore, SCV loss, but not total brain volume and T2 lesion volume, was a strong predictor of EDSS score worsening over time (p < 0.05). The mean annual rate of SCV loss was the strongest MRI predictor for the mean annual EDSS score change of both RRMS and SPMS separately, while correlating stronger in SPMS. Every 1% increase of the annual SCV loss rate was associated with an extra 28% risk increase of disease progression in the following year in both groups.

Conclusion SCV loss over time relates to the number of clinical relapses in RRMS, but overall does not differ between RRMS and SPMS. SCV proved to be a strong predictor of physical disability and disease progression, indicating that SCV may be a suitable marker for monitoring disease activity and severity.

Glossary

EDSS=
Expanded Disability Status Scale;
LMER=
linear mixed-effects regression;
MLR=
multiple linear regression;
MS=
multiple sclerosis;
RRMS=
relapsing-remitting multiple sclerosis;
SC=
spinal cord;
SCV=
spinal cord volume;
SPMS=
secondary progressive multiple sclerosis;
T2LV=
T2 lesion volume;
T25-FW=
Timed 25-Foot Walk;
TBV=
total brain volume

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial, page 157

  • Received December 1, 2017.
  • Accepted in final form April 19, 2018.
  • © 2018 American Academy of Neurology
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