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The utility of cerebrospinal fluid analysis in patients with multiple sclerosis

Abstract

Diagnosis of multiple sclerosis (MS) requires the exclusion of other possible diagnoses. For this reason, the cerebrospinal fluid (CSF) should be routinely analysed in patients with a first clinical event suggestive of MS. CSF analysis is no longer mandatory for diagnosis of relapsing–remitting MS, as long as MRI diagnostic criteria are fulfilled. However, caution is required in diagnosing MS in patients with negative MRI findings or in the absence of CSF analysis, as CSF investigation is useful to eliminate other causes of disease. The detection of oligoclonal IgG bands in CSF has potential prognostic value and is helpful for clinical decision-making. In addition, CSF analysis is important for research into the pathogenesis of MS. Pathophysiological and neurodegenerative findings of inflammation in MS have been derived from CSF investigations. Novel CSF biomarkers, though not yet validated, have been identified for diagnosis of MS and for ascertaining disease activity, prognosis and response to treatment, and are likely to increase in number with modern detection techniques. In this Review, we summarize CSF findings that shed light on the differential diagnosis of MS, and highlight the potential of novel biomarkers for this disease that could advance understanding of its pathophysiology.

Key Points

  • Cerebrospinal fluid (CSF) analysis is used to exclude other diseases in the differential diagnosis of multiple sclerosis (MS)

  • Detection of oligoclonal IgG bands and elevated CXCL13 levels in the CSF can be used to make a prognosis and predict subsequent relapse in patients with clinically isolated syndrome

  • Investigation of CSF has helped to elucidate inflammatory and neurodegenerative mechanisms in MS

  • New candidate markers for MS have been described in CSF, but require validation in large cohorts of patients

  • Standardized assays to identify and quantify potential MS markers in CSF are needed to enable comparisons between studies and cohorts of patients

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Figure 1: Historical overview of developments in CSF examination.
Figure 2: Sources of CSF proteins.
Figure 3: Source of biomarkers in the pathophysiology of multiple sclerosis.

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Acknowledgements

M.Stangel is supported by the Bundesministerium für Bildung und Forschung (Clinical Competence Network Multiple Sclerosis) and the Deutsche Forschungsgemeinschaft. E. Meinl is supported by the Deutsche Forschungsgemeinschaft (SFB TR 128), the Bundesministerium für Bildung und Forschung, the Gemeinnützige-Hertie Stiftung and the Verein zur Therapieforschung für MS Kranke. O. Stüve is supported by grants from the Department of Veterans Affairs, the National Multiple Sclerosis Society and the Doris Duke Charitable Foundation. H. Tumani is supported by the Hertie-Stiftung, Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung and the University of Ulm, Germany.

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M. Stangel, S. Fredrikson, E. Meinl, A. Petzold, O. Stüve and H. Tumani researched data for the article, and contributed to discussion of the content and writing of the article. All authors contributed substantially to review and/or editing of the manuscript before submission.

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Correspondence to Martin Stangel.

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M. Stangel has received honoraria for scientific lectures or consultancy from the following companies: Bayer Healthcare, Biogen Idec, CSL Behring, Grifols, Merck Serono, Novartis, Sanofi Aventis and Teva. S. Fredrikson has received honoraria for lectures, educational activities or consultancy from the following companies: Allergan, Bayer, Biogen Idec, Genzyme Virotec, Merck Serono, Novartis, Sanofi Aventis and Teva. E. Meinl has received honoraria from Teva and Novartis and grant support from Novartis. O. Stüve has been a consultant for the following companies: Teva, Biogen Idec, Genzyme Virotec, Novartis and Sanofi Aventis. H. Tumani serves on a scientific advisory board, is a consultant for, and/or has received funding from the following companies: Bayer Healthcare, Biogen Idec, Genzyme Virotec, Merck Serono, Novartis, Roche and Teva. A. Petzold holds patent number WO2012/005588.

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Stangel, M., Fredrikson, S., Meinl, E. et al. The utility of cerebrospinal fluid analysis in patients with multiple sclerosis. Nat Rev Neurol 9, 267–276 (2013). https://doi.org/10.1038/nrneurol.2013.41

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