Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients
- Equal contributors
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
Journal of Neuroinflammation 2012, 9:14 doi:10.1186/1742-2094-9-14Published: 19 January 2012
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.
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.
Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%).
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.
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.