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Clinico-radiological dissociation of disease activity in MS patients: frequency and clinical relevance

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Abstract

Objective

To investigate the prevalence and clinical relevance regarding disability progression in multiple sclerosis patients with a dissociation in clinical and radiological disease expression.

Methods

We prospectively selected patients with early relapsing–remitting multiple sclerosis (MS) or a clinically isolated syndrome (CIS) from the Amsterdam MS cohort. Patients underwent clinical examination at baseline, after 2 years, 6 years and a subset also after 11 years, including the Expanded Disability Status Scale (EDSS), 25-foot walk test (25-FWT) and 9-hole peg test (9-HPT). Brain and spinal cord MRI scans were obtained at baseline and after 2 years. Two years after baseline, patients with dissociation in their clinical and radiological disease progression were identified as: (1) patients with high clinical disease activity (defined by relapses) and low radiological disease activity (defined by white-matter lesions on T2-weighted imaging); or (2) patients with low clinical disease activity and high radiological disease activity. Binary logistic regression analyses were performed to predict disability progression after 6 and 11 years of follow-up. Patients with low clinical and low radiological disease activity were used as the reference group.

Results

The prevalence of clinico-radiological dissociation was low (6.4% had high clinical and low radiological disease activity and 5.1% had a combination of low clinical and high radiological disease activity) compared to 88.5% of patients without a dissociation. Patients with a dissociation of clinical and radiological disease activity did not show a statistically significant difference in risk of disability progression after 6 and 11 years.

Conclusions

A clinico-radiological dissociation is rather a rare phenomenon in MS patients. The clinical relevance of such a dissociation regarding the prediction of disability progression is questionable.

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Data availability

Data were transparent for all authors.

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Funding

The MS Center Amsterdam is funded by a program grant (14-358e) from the Stichting voor MS Research (Voorschoten, The Netherlands). None of the funders had any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Author information

Author notes

  1. Nina L. van Faals and Iris Dekker contributed equally to the manuscript.

Authors and Affiliations

  1. Department of Neurology, Amsterdam UMC, Location VU University Medical Center, Amsterdam, The Netherlands

    Nina L. van Faals, Iris Dekker, Lisanne J. Balk, Bernard M. J. Uitdehaag & Joep Killestein

  2. Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location VU University Medical Center, Amsterdam, The Netherlands

    Iris Dekker, Bastiaan Moraal, Frederik Barkhof & Mike P. Wattjes

  3. University College London Queen Square Institute of Neurology, Faculty of Brain Sciences, London, UK

    Frederik Barkhof

  4. National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC), London, UK

    Frederik Barkhof

  5. Department of Diagnostic and Interventional Neuroradiology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany

    Mike P. Wattjes

Authors
  1. Nina L. van Faals
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  2. Iris Dekker
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  3. Lisanne J. Balk
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  4. Bastiaan Moraal
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  5. Frederik Barkhof
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  6. Bernard M. J. Uitdehaag
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  7. Joep Killestein
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  8. Mike P. Wattjes
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Contributions

Conceptualization and design of the study: NLF, ID, MPW. Acquisition and analysis of data: NLF, ID, MPW, BM, FB. Statistical analysis: ID, LJB. Drafting of a significant portion of the manuscript and table: all authors.

Corresponding author

Correspondence to Mike P. Wattjes.

Ethics declarations

Conflicts of interest

N.L. van Faals, L.J. Balk, B. Moraal have nothing to disclose. I. Dekker received speaking honoraria from Roche. F. Barkhof serves as editorial board member of Brain, Neuroradiology, Neurology, Multiple Sclerosis Journal and Radiology. He has accepted personal fees from Springer, Bayer, Biogen, Roche, Apitope Ltd, IXICO ltd, Novartis, GeNEuro. Grants from Novartis, TEVA, Merck, Biogen, IMI-EU, GE Healthcare, UK MS Society, Dutch MS research foundation, NWO, NIHR. FB is supported by the NIHR UCLH biomedical research centre. B.M.J. Uitdehaag has received consultancy fees and/or research support from Biogen Idec, Sanofi Genzyme, Merck Serono, Roche and Teva. J. Killestein reports grants and personal fees from Biogen Idec, Novartis, Merck Serono, TEVA, Genzyme, Roche, outside the submitted work. M.P. Wattjes reports personal consultancy and speaking fees from Biogen, Novartis, Janssen, Roche, Celgene, IXICO, Sanofi Genzyme, Bayer Healthcare, Biologix, Genilac, Merck Serono and Teva.

Ethical approval

The study was approved by the Institutional review board of the VU University Medical Center, Amsterdam, The Netherlands.

Consent to participate

Written informed consent was obtained from all participants for the use of the clinical, laboratory and imaging data for research and teaching purposes.

Consent for publication

Written informed consent was obtained from all participants for publishing the data.

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van Faals, N.L., Dekker, I., Balk, L.J. et al. Clinico-radiological dissociation of disease activity in MS patients: frequency and clinical relevance. J Neurol 267, 3287–3291 (2020). https://doi.org/10.1007/s00415-020-09991-1

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  • DOI: https://doi.org/10.1007/s00415-020-09991-1

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