Cerebrospinal fluid findings in aquaporin-4 antibody positive neuromyelitis optica: Results from 211 lumbar punctures
Introduction
Neuromyelitis optica (Devic syndrome, NMO) is a severely disabling disorder of the central nervous system (CNS) of putative autoimmune aetiology, which predominantly affects the optic nerves and the spinal cord [1]. For many years, NMO was considered to be a subtype of multiple sclerosis (MS). Recently, however, it was shown that 60–80% of NMO patients are positive for antibodies to aquaporin-4, the most abundant water channel in the CNS [2], [3], [4], [5]. The discovery of this new serum reactivity (termed NMO-IgG or AQP4-Ab) rendered it possible to distinguish NMO from classical MS by means of a laboratory test for the first time. Subsequently, the demonstration of both NMO-like CNS lesions and clinical disease following passive transfer of AQP4-Ab-positive sera in several independent animal studies provided strong evidence for a pathogenic role of AQP4-Ab in vivo [6], [7], [8], [9], [10], [11], [12].
So far, only very little is known about cerebrospinal fluid (CSF) findings in patients with AQP4-Ab positive NMO. Previous studies did not take into account the patients AQP4-Ab status [1], [13], [14], [15], [16], were based on small patient numbers [14], [15], [17], [18], and/or did not include Caucasian patients [17]. Moreover, all of these studies investigated only a few selected CSF parameters [1], [14], [15], [16], [17], [18].
In the present study we systematically and comprehensively analysed the results of 211 lumbar punctures (LP) from a clinically and serologically homogeneous cohort of 89 mainly Caucasian patients with AQP4-Ab positive NMO and its formes frustes, longitudinally extensive transverse myelitis (LETM) and optic neuritis (ON).
Section snippets
Patients
Results from 211 lumbar punctures in 89 patients with AQP4-Ab positive neuromyelitis optica spectrum disorders (NMOSD) (median age, 39.5 years, range, 14–79; male:female = 1:12.1) were analysed retrospectively. All patients were diagnosed with NMOSD at various German, Austrian and Italian university hospitals. The diagnosis of NMO was established according to Wingerchuk's revised 2006 criteria [19]. LETM was defined as myelitis extending over three or more vertebral segments as detected by
Cellular immune response
An increased CSF white cell count (WCC) was found in 98/194 (50.5%) samples examined, with a median of 19 cells/μl (range, 6–380). However, severe pleocytosis, as defined by a CSF WCC > = 100 cells/μl, was present only in 12/194 (6.2%) samples (median, 139; range, 103–380). Of these 12 samples, 11 were taken during relapse (the disease status in the remaining patient is unknown), and 9 were obtained from untreated patients. Lymphocytes were detectable in 114/117 (97.4%) samples (up to 100% of all
Discussion
In this study, we demonstrate a differential pattern of CSF pathology in AQP4-Ab positive NMOSD as compared to that reported in classic multiple sclerosis (MS) [22], [25]. Our findings provide further evidence in favour of the hypothesis of AQP4-Ab positive NMO representing a disease in its own right rather than a subtype of MS [26], [27], [28], [29].
Most strikingly, 148/177 (84%) samples showed no signs of intrathecal synthesis (IS) of IgG as indicated by absence of CSF-restricted OCBs. This
Acknowledgements
This work was supported by a Research Fellowship from the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) to S.J., by research grants from Bayer Schering Healthcare and Merck Serono to S.J. and B.W., and by a grant from the German Research Foundation (DFG Exc 257) to F.P. We thank Jacqueline Gosink, PhD, and Jason Millward, PhD, for copy-editing.
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