Importance of cerebrospinal fluid analysis in the era of McDonald 2010 criteria: a German–Austrian retrospective multicenter study in patients with a clinically isolated syndrome

Journal of Neurology, Oct 2016

The majority of patients presenting with a first clinical symptom suggestive of multiple sclerosis (MS) do not fulfill the MRI criteria for dissemination in space and time according to the 2010 revision of the McDonald diagnostic criteria for MS and are thus classified as clinically isolated syndrome (CIS). To re-evaluate the utility of cerebrospinal fluid (CSF) analysis in the context of the revised McDonald criteria from 2010, we conducted a retrospective multicenter study aimed at determining the prevalence and predictive value of oligoclonal IgG bands (OCBs) in patients with CIS. Patients were recruited from ten specialized MS centers in Germany and Austria. We collected data from 406 patients; at disease onset, 44/406 (11 %) fulfilled the McDonald 2010 criteria for MS. Intrathecal IgG OCBs were detected in 310/362 (86 %) of CIS patients. Those patients were twice as likely to convert to MS according to McDonald 2010 criteria as OCB-negative individuals (hazard ratio = 2.1, p = 0.0014) and in a shorter time period of 25 months (95 % CI 21–34) compared to 47 months in OCB-negative individuals (95 % CI 36–85). In patients without brain lesions at first attack and presence of intrathecal OCBs (30/44), conversion rate to MS was 60 % (18/30), whereas it was only 21 % (3/14) in those without OCBs. Our data confirm that in patients with CIS the risk of conversion to MS substantially increases if OCBs are present at onset. CSF analysis definitely helps to evaluate the prognosis in patients who do not have MS according to the revised McDonald criteria.

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Importance of cerebrospinal fluid analysis in the era of McDonald 2010 criteria: a German–Austrian retrospective multicenter study in patients with a clinically isolated syndrome

Importance of cerebrospinal fluid analysis in the era of McDonald 2010 criteria: a German-Austrian retrospective multicenter study in patients with a clinically isolated syndrome Andre´ M. Huss 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Steffen Halbgebauer 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Patrick O¨ ckl 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Corinna Trebst 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Annette Spreer 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Nadja Borisow 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Andrea Harrer 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Isabel Brecht 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Bettina Balint 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Oliver Stich 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Sabine Schlegel 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Nele Retzlaff 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Alexander Winkelmann 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Romy Roesler 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Florian Lauda 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 O¨ zlem Yildiz 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Elke Voß 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Rainer Muche 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Sebastian Rauer 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Florian Then Bergh 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Markus Otto 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Friedemann Paul 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Brigitte Wildemann 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Jo¨ rg Kraus 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Klemens Ruprecht 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Martin Stangel 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Mathias Buttmann 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Uwe K. Zettl 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Hayrettin Tumani 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 0 University of Go ̈ttingen , Go ̈ttingen , Germany 1 University of Freiburg , Freiburg , Germany 2 Hannover Medical School , Hannover , Germany 3 UCL Institute of Neurology , London , UK 4 University of Leipzig , Leipzig , Germany 5 Department of Neurology, University of Ulm , Oberer Eselsberg 45, 89081 Ulm , Germany 6 Neuroimmunological Section, Department of Neurology, University of Rostock , Rostock , Germany 7 University of Heidelberg , Heidelberg , Germany 8 (OCBs) in patients with CIS. Patients were recruited from ten specialized MS centers in Germany and Austria. We collected data from 406 patients; at disease onset, 44/406 (11 %) fulfilled the McDonald 2010 criteria for MS. Intrathecal IgG OCBs were detected in 310/362 (86 %) of CIS patients. Those patients were twice as likely to convert to MS according to McDonald 2010 criteria as OCB-neg- ative individuals (hazard ratio = 2.1, p = 0.0014) and in a shorter time period of 25 months (95 % CI 21-34) com- pared to 47 months in OCB-negative individuals (95 % CI 36-85). In patients without brain lesions at first attack and presence of intrathecal OCBs (30/44) , conversion rate to MS was 60 % (18/30), whereas it was only 21 % (3/14) in 9 University of Wu ̈rzburg , Wu ̈rzburg , Germany 10 University of Du ̈sseldorf , Du ̈sseldorf , Germany 11 Department of Neurology, Paracelsus Medical University Salzburg , Salzburg , Austria 12 Department of Laboratory Medicine, Paracelsus Medical University Salzburg , Salzburg , Austria 13 Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine, Charite ́-Universita ̈tsmedizin Berlin , Berlin , Germany 14 Department of Neurology and Clinical and Experimental Multiple Sclerosis Research Center, Charite ́- Universita ̈tsmedizin Berlin , Berlin , Germany 15 NeuroCure Clinical Research Center, Charite ́- Universita ̈tsmedizin Berlin , Berlin , Germany The majority of patients presenting with a first clinical symptom suggestive of multiple sclerosis (MS) do not fulfill the MRI criteria for dissemination in space and time according to the 2010 revision of the McDonald diagnostic criteria for MS and are thus classified as clinically isolated syndrome (CIS). To re-evaluate the utility of cerebrospinal fluid (CSF) analysis in the context of the revised McDonald criteria from 2010, we conducted a retrospective multicenter study aimed at determining the prevalence and predictive value of oligoclonal IgG bands U. K. Zettl and H. Tumani contributed equally to this work. - & Hayrettin Tumani those without OCBs. Our data confirm that in patients with CIS the risk of conversion to MS substantially increases if OCBs are present at onset. CSF analysis definitely helps to evaluate the prognosis in patients who do not have MS according to the revised McDonald criteria. Multiple sclerosis (MS) is a chronic inflammatory disease mainly characterized by demyelination and axonal loss [1]. A formal diagnosis of MS is based on clinical and radiological findings with an increasing role of MRI examinations as established in the 2010 revision of the so-called McDonald diagnostic criteria [2]. Here, cerebrospinal fluid (CSF) analysis, and in particular the detection of intrathecal IgG oligoclonal bands (OCBs), is a supportive (...truncated)


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André M. Huss, Steffen Halbgebauer, Patrick Öckl, Corinna Trebst, Annette Spreer, Nadja Borisow, Andrea Harrer, Isabel Brecht, Bettina Balint, Oliver Stich, Sabine Schlegel, Nele Retzlaff, Alexander Winkelmann, Romy Roesler, Florian Lauda, Özlem Yildiz, Elke Voß, Rainer Muche, Sebastian Rauer, Florian Then Bergh, Markus Otto, Friedemann Paul, Brigitte Wildemann, Jörg Kraus, Klemens Ruprecht, Martin Stangel, Mathias Buttmann, Uwe K. Zettl, Hayrettin Tumani. Importance of cerebrospinal fluid analysis in the era of McDonald 2010 criteria: a German–Austrian retrospective multicenter study in patients with a clinically isolated syndrome, Journal of Neurology, 2016, pp. 2499-2504, Volume 263, Issue 12, DOI: 10.1007/s00415-016-8302-1