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

Journal of Neuroinflammation

Friedemann Paul^1,15  Orhan Aktas^2,21  Hans P Hartung^2,21  Christian Wilke^1,18  Jörn P Sieb^1,12  Christian Veauthier^1,12  Imke Metz^2,20  Uwe K Zettl U^2,22  Alexander Winkelmann^2,22  Christoph Münch²  Sabine Niehaus⁹  Paulus S Rommer^2,22  Martin Liebetrau^2,29  Stefan Langel^2,24  Tobias Boettcher⁸  Florian Then Bergh^2,26  Klaus P Wandinger^1,13  Peter Kern^1,14  Ulf Ziemann⁴  Hannah Pellkofer^1,16  Reinhard Reuss⁶  Ulrich Hofstadt-van Oy⁶  Kersten Guthke^2,28  Christian Zentner^1,19  Barbara Ettrich^2,26  Oliver Neuhaus^1,10  Jürgen H Faiss^1,14  Sven Schippling³  Frank Hoffmann^1,19  Martin Marziniak^1,11  Martin Stangel⁵  Corinna Trebst⁵  Arthur Melms^2,25  Hayrettin Tumani^2,27  Christoph A Mayer⁴  Florian Lauda^2,27  Ralf A Linker¹  Bernhard Hemmer^1,17  Kerstin Hellwig¹  Johannes Brettschneider^2,27  Achim Berthele^1,17  Christoph Kleinschnitz⁷  Ingo Kleiter¹  Christian Geis⁷  Marius Ringelstein^2,21  Tania Kuempfel^1,16  Brigitte Wildemann^2,23  Klemens Ruprecht²  Sven Jarius^2,23 

[1] Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany;Department of Neurology, Charité - University Medicine Berlin, Berlin, Germany;Department of Neurology, and Institute for Neuroimmunology and Clinical Multiple Sclerosis Research, University Medical Center, Hamburg, Germany;Department of Neurology, Goethe University Frankfurt, Frankfurt, Germany;Department of Neurology, Hannover Medical School, Hannover, Germany;Department of Neurology, Klinikum Bayreuth, Bayreuth, Germany;Department of Neurology, University of Würzburg, Würzburg, Germany;Department of Neurology, Dietrich Bonhoeffer Klinikum Neubrandenburg, Neubrandenburg, Germany;Department of Neurology, Klinikum Dortmund, Dortmund, Germany;Department of Neurology, Kliniken Landkreis Sigmaringen GmbH, Sigmaringen, Germany;Department of Neurology, University of Münster, Münster, Germany;Department of Neurology, Hanse-Klinikum Stralsund, Stralsund, Germany;Institute of Experimental Neuroimmunology, affiliated to Euroimmun Lübeck, Lübeck, Germany;Department of Neurology, Asklepios Hospital Teupitz, Teupitz, Germany;Neurocure, Charité - University Medicine Berlin, Berlin, Germany;Institute of Clinical Neuroimmunology, Ludwig Maximilian University Munich, Munich, Germany;Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Germany;Department of Neurology, Helios Vogtland-Klinikum Plauen, Plauen, Germany;Department of Neurology, Hospital Martha-Maria Halle, Halle, Germany;Department of Neuropathology, University of Göttingen, Göttingen, Germany;Department of Neurology, Heinrich Heine University, Düsseldorf, Germany;Department of Neurology, University of Rostock, Rostock, Germany;Division of Molecular Neuroimmunology, Department of Neurology, University of Heidelberg, Heidelberg, Germany;Department of Neurology, Rheinhessen-Fachklinik Alzey, Alzey, Germany;Department of Neurology, University of Tübingen, Tübingen, Germany;Department of Neurology, University of Leipzig, Leipzig, Germany;Department of Neurology, University of Ulm, Ulm, Germany;Department of Neurology, Klinikum Görlitz, Görlitz, Germany;Department of Neurology, Dr. Horst Schmidt Hospital Wiesbaden, Wiesbaden, Germany

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

Others  :  1212859
DOI  :  10.1186/1742-2094-9-14

 received in 2011-09-23, accepted in 2012-01-19,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Jarius et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

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