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Editorial |

Does Aquaporin-4–Seronegative Neuromyelitis Optica Exist?

Michael Levy, MD, PhD1
[+] Author Affiliations
1Department of Neurology, Johns Hopkins University, Baltimore, Maryland
JAMA Neurol. 2014;71(3):271-272. doi:10.1001/jamaneurol.2013.5865.
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With the improvement in anti–aquaporin-4 (AQP4) assay sensitivity to near 90%,1 the concept of seronegative neuromyelitis optica (NMO) is being challenged. The widely accepted criteria for NMO proposed2 in 1999 and revised3 in 2006 define NMO as a disease localized to the optic nerves and spinal cord, which is not multiple sclerosis (MS). The anti-AQP4 antibody has always been a very highly specific biomarker for NMO but, owing to insensitive assays, seropositivity was initially considered only a supportive criterion. Seronegative NMO was intended to represent the same disease process as seropositive NMO but, for whatever reason, the anti-AQP4 antibody was not detectable at the time. During the past 8 years since the anti-AQP4 antibody biomarker was discovered and linked to NMO, the research field has focused intensely on the role of AQP4 as an immunopathogenic target.4 Supported by incremental advancements in the anti-AQP4 biomarker assay, the understanding of true NMO is expanding its localization to brainstem and cortical disease, while narrowing its population base to those who are seropositive for the anti-AQP4 antibody.5 That leaves neuroimmunologists with the question of whether a seronegative NMO disease actually exists?

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