Double-negative neuromyelitis optica spectrum disorder

Mult Scler. 2023 Oct;29(11-12):1353-1362. doi: 10.1177/13524585231199819. Epub 2023 Sep 23.

Abstract

Most patients with neuromyelitis optica spectrum disorders (NMOSD) test positive for aquaporin-4 antibody (AQP4-IgG) or myelin oligodendrocyte glycoprotein antibodies (MOG-IgG). Those who are negative are termed double-negative (DN) NMOSD and may constitute a diagnostic and therapeutic challenge. DN NMOSD is a syndrome rather than a single disease, ranging from a (postinfectious) monophasic illness to a more chronic syndrome that can be indistinguishable from AQP4-IgG+ NMOSD or develop into other mimics such as multiple sclerosis. Thus, underlying disease mechanisms are likely to be heterogeneous. This topical review aims to (1) reappraise antibody-negative NMOSD definition as it has changed over time with the development of the AQP4 and MOG-IgG assays; (2) outline clinical characteristics and the pathophysiological nature of this rare entity by contrasting its differences and similarities with antibody-positive NMOSD; (3) summarize laboratory characteristics and magnetic resonance imaging findings of DN NMOSD; and (4) discuss the current treatment for DN NMOSD.

Keywords: AQP4-IgG; MOG-IgG; double seronegative; multiple sclerosis; neuromyelitis optica spectrum disorder.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aquaporin 4
  • Autoantibodies
  • Humans
  • Immunoglobulin G
  • Multiple Sclerosis*
  • Myelin-Oligodendrocyte Glycoprotein
  • Neuromyelitis Optica* / diagnostic imaging
  • Neuromyelitis Optica* / therapy

Substances

  • Aquaporin 4
  • Myelin-Oligodendrocyte Glycoprotein
  • Immunoglobulin G
  • Autoantibodies