Abstract
Background
Neuromyelitis optica (NMO, Devic disease) is a severely disabling autoimmune disorder
of the CNS, which was considered a subtype of multiple sclerosis (MS) for many decades.
Recently, however, highly specific serum autoantibodies (termed NMO-IgG or AQP4-Ab)
have been discovered in a subset (60–80%) of patients with NMO. These antibodies were
subsequently shown to be directly involved in the pathogenesis of the condition. AQP4-Ab
positive NMO is now considered an immunopathogenetically distinct disease in its own
right. However, to date little is known about the cerebrospinal fluid (CSF) in AQP4-Ab
positive NMO.
Objective
To describe systematically the CSF profile of AQP4-Ab positive patients with NMO or
its formes frustes, longitudinally extensive myelitis and optic neuritis.
Material and methods
Cytological and protein biochemical results from 211 lumbar punctures in 89 AQP4-Ab
positive patients of mostly Caucasian origin with neuromyelitis optica spectrum disorders
(NMOSD) were analysed retrospectively.
Results
CSF-restricted oligoclonal IgG bands, a hallmark of MS, were absent in most patients.
If present, intrathecal IgG (and, more rarely, IgM) synthesis was low, transient,
and, importantly, restricted to acute relapses. CSF pleocytosis was present in around
50% of samples, was mainly mild (median, 19 cells/μl; range 6–380), and frequently included neutrophils, eosinophils, activated
lymphocytes, and/or plasma cells. Albumin CSF/serum ratios, total protein and CSF
L-lactate levels correlated significantly with disease activity as well as with the
length of the spinal cord lesions in patients with acute myelitis. CSF findings differed
significantly between patients with acute myelitis and patients with acute optic neuritis
at the time of LP. Pleocytosis and blood CSF barrier dysfunction were also present
during remission in some patients, possibly indicating sustained subclinical disease
activity.
Conclusion
AQP4-Ab positive NMOSD is characterized by CSF features that are distinct from those
in MS. Our findings are important for the differential diagnosis of MS and NMOSD and
add to our understanding of the immunopathogenesis of this devastating condition.
Abbreviations:
AQP4 (aquaporin-4), AQP4-Ab (aquaporin-4 antibody), CBA (cell based assay), CSF (cerebro-spinal fluid), IHC (immunohistochemistry), LETM (longitudinally extensive transverse myelitis), LP (lumbar puncture), NMO (neuromyelitis optica), NMOSD (neuromyelitis optica spectrum disorders), NMO-IgG (neuromyelitis optica immunoglobulin G), OCB (oligoclonal bands), QAlb (albumin CSF/serum ratio), QIgG (IgG CSF/serum ratio), QIgM (IgM CSF/serum ratio), QIgA (IgA CSF/serum ratio), rON (recurrent optic neuritis)Keywords
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Article info
Publication history
Published online: May 09, 2011
Accepted:
March 24,
2011
Received in revised form:
March 20,
2011
Received:
February 6,
2011
Identification
Copyright
© 2011 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
