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Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients

Sven Jarius1, Klemens Ruprecht2, Brigitte Wildemann1, Tania Kuempfel3, Marius Ringelstein4, Christian Geis5, Ingo Kleiter67, Christoph Kleinschnitz5, Achim Berthele8, Johannes Brettschneider9, Kerstin Hellwig7, Bernhard Hemmer8, Ralf A Linker107, Florian Lauda9, Christoph A Mayer11, Hayrettin Tumani9, Arthur Melms12, Corinna Trebst13, Martin Stangel13, Martin Marziniak14, Frank Hoffmann15, Sven Schippling16, Jürgen H Faiss17, Oliver Neuhaus18, Barbara Ettrich19, Christian Zentner15, Kersten Guthke20, Ulrich Hofstadt-van Oy21, Reinhard Reuss21, Hannah Pellkofer3, Ulf Ziemann11, Peter Kern17, Klaus P Wandinger1622, Florian Then Bergh19, Tobias Boettcher23, Stefan Langel24, Martin Liebetrau25, Paulus S Rommer26, Sabine Niehaus27, Christoph Münch2, Alexander Winkelmann26, Uwe K Zettl U26, Imke Metz28, Christian Veauthier29, Jörn P Sieb29, Christian Wilke30, Hans P Hartung4, Orhan Aktas4 and Friedemann Paul31*

Author Affiliations

1 Division of Molecular Neuroimmunology, Department of Neurology, University of Heidelberg, Heidelberg, Germany

2 Department of Neurology, Charité - University Medicine Berlin, Berlin, Germany

3 Institute of Clinical Neuroimmunology, Ludwig Maximilian University Munich, Munich, Germany

4 Department of Neurology, Heinrich Heine University, Düsseldorf, Germany

5 Department of Neurology, University of Würzburg, Würzburg, Germany

6 Department of Neurology, University of Regensburg, Regensburg, Germany

7 Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany

8 Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Germany

9 Department of Neurology, University of Ulm, Ulm, Germany

10 Department of Neurology, Friedrich Alexander University, Erlangen, Germany

11 Department of Neurology, Goethe University Frankfurt, Frankfurt, Germany

12 Department of Neurology, University of Tübingen, Tübingen, Germany

13 Department of Neurology, Hannover Medical School, Hannover, Germany

14 Department of Neurology, University of Münster, Münster, Germany

15 Department of Neurology, Hospital Martha-Maria Halle, Halle, Germany

16 Department of Neurology, and Institute for Neuroimmunology and Clinical Multiple Sclerosis Research, University Medical Center, Hamburg, Germany

17 Department of Neurology, Asklepios Hospital Teupitz, Teupitz, Germany

18 Department of Neurology, Kliniken Landkreis Sigmaringen GmbH, Sigmaringen, Germany

19 Department of Neurology, University of Leipzig, Leipzig, Germany

20 Department of Neurology, Klinikum Görlitz, Görlitz, Germany

21 Department of Neurology, Klinikum Bayreuth, Bayreuth, Germany

22 Institute of Experimental Neuroimmunology, affiliated to Euroimmun Lübeck, Lübeck, Germany

23 Department of Neurology, Dietrich Bonhoeffer Klinikum Neubrandenburg, Neubrandenburg, Germany

24 Department of Neurology, Rheinhessen-Fachklinik Alzey, Alzey, Germany

25 Department of Neurology, Dr. Horst Schmidt Hospital Wiesbaden, Wiesbaden, Germany

26 Department of Neurology, University of Rostock, Rostock, Germany

27 Department of Neurology, Klinikum Dortmund, Dortmund, Germany

28 Department of Neuropathology, University of Göttingen, Göttingen, Germany

29 Department of Neurology, Hanse-Klinikum Stralsund, Stralsund, Germany

30 Department of Neurology, Helios Vogtland-Klinikum Plauen, Plauen, Germany

31 Neurocure, Charité - University Medicine Berlin, Berlin, Germany

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Journal of Neuroinflammation 2012, 9:14  doi:10.1186/1742-2094-9-14

Published: 19 January 2012

Abstract

Background

The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity.

Objective

To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus.

Methods

Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%).

Results

Seropositive patients were found to be predominantly female (p < 0.0003), to more often have signs of co-existing autoimmunity (p < 0.00001), and to experience more severe clinical attacks. A visual acuity of ≤ 0.1 during acute optic neuritis (ON) attacks was more frequent among seropositives (p < 0.002). Similarly, motor symptoms were more common in seropositive patients, the median Medical Research Council scale (MRC) grade worse, and MRC grades ≤ 2 more frequent, in particular if patients met the 2006 revised criteria (p < 0.005, p < 0.006 and p < 0.01, respectively), the total spinal cord lesion load was higher (p < 0.006), and lesions ≥ 6 vertebral segments as well as entire spinal cord involvement more frequent (p < 0.003 and p < 0.043). By contrast, bilateral ON at onset was more common in seronegatives (p < 0.007), as was simultaneous ON and myelitis (p < 0.001); accordingly, the time to diagnosis of NMO was shorter in the seronegative group (p < 0.029). The course of disease was more often monophasic in seronegatives (p < 0.008). Seropositives and seronegatives did not differ significantly with regard to age at onset, time to relapse, annualized relapse rates, outcome from relapse (complete, partial, no recovery), annualized EDSS increase, mortality rate, supratentorial brain lesions, brainstem lesions, history of carcinoma, frequency of preceding infections, oligoclonal bands, or CSF pleocytosis. Both the time to relapse and the time to diagnosis was longer if the disease started with ON (p < 0.002 and p < 0.013). Motor symptoms or tetraparesis at first myelitis and > 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome.

Conclusion

This study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients.

Keywords:
Neuromyelitis optica; Devic disease; Devic syndrome; longitudinally extensive transverse myelitis; recurrent optic neuritis; NMO-IgG; aquaporin-4 (AQP4) antibody; epidemiology; clinical features; magnetic resonance imaging; cerebrospinal fluid