title: Cerebrospinal fluid findings in aquaporin-4 antibody positive neuromyelitis optica: results from 211 lumbar punctures.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Molecular Neuroimmunology, Department of Neurology, University of Heidelberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Jarius
authors.forename: F
authors.initials: F
authors.lastname: Paul
authors.forename: D
authors.initials: D
authors.lastname: Franciotta
authors.forename: K
authors.initials: K
authors.lastname: Ruprecht
authors.forename: M
authors.initials: M
authors.lastname: Ringelstein
authors.forename: R
authors.initials: R
authors.lastname: Bergamaschi
authors.forename: P
authors.initials: P
authors.lastname: Rommer
authors.forename: I
authors.initials: I
authors.lastname: Kleiter
authors.forename: O
authors.initials: O
authors.lastname: Stich
authors.forename: R
authors.initials: R
authors.lastname: Reuss
authors.forename: S
authors.initials: S
authors.lastname: Rauer
authors.forename: U K
authors.initials: UK
authors.lastname: Zettl
authors.forename: K P
authors.initials: KP
authors.lastname: Wandinger
authors.forename: A
authors.initials: A
authors.lastname: Melms
authors.forename: O
authors.initials: O
authors.lastname: Aktas
authors.forename: W
authors.initials: W
authors.lastname: Kristoferitsch
authors.forename: B
authors.initials: B
authors.lastname: Wildemann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000418:Albumins / Q000134:cerebrospinal fluid; D000906:Antibodies / Q000097:blood / Q000134:cerebrospinal fluid* / Q000145:classification; D051401:Aquaporin 4 / Q000276:immunology*; D001812:Blood-Brain Barrier / Q000503:physiopathology; D002556:Cerebrospinal Fluid Proteins / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000134:cerebrospinal fluid; D007958:Leukocyte Count; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009471:Neuromyelitis Optica / Q000134:cerebrospinal fluid* / Q000473:pathology; D043025:Oligoclonal Bands / Q000097:blood / Q000134:cerebrospinal fluid; D012709:Serum Albumin / Q000378:metabolism; D013129:Spinal Puncture / Q000379:methods; D055815:Young Adult
chemical_list: D000418:Albumins; D000906:Antibodies; D051401:Aquaporin 4; D002556:Cerebrospinal Fluid Proteins; D043025:Oligoclonal Bands; D012709:Serum Albumin; D019344:Lactic Acid