Fig. 1

Pathogenesis of neuromyelitis optica spectrum disorder (NMOSD) (1–6) and clinical findings for the patient (7–11). 1 Aquaporin-4 immunoglobulin G (AQP4-IgG) accesses the central nervous system at areas of increased blood-brain barrier (BBB) permeability or injury or across endothelial cells by transcytosis. The antibody binds selectively to AQP4 antigen on astrocyte foot processes. The BBB is formed by various components, some of which are illustrated: endothelial cells and astrocyte foot processes. 2 The antigen-antibody binding leads to complement activation and downregulation of the AQP4 water channel. 3 Activated complement increases BBB permeability and leads to leukocyte infiltration, particularly neutrophils and eosinophils. 4 Leukocyte degranulation results in astrocyte death. 5 Chemokines are released from leukocytes and dying astrocytes and attract macrophages. 6 Macrophages produce proinflammatory substances and phagocytose the myelin, resulting in the death of oligodendrocytes (myelin-producing cells) and neurons. 7 Microparticle (MP) numbers of antibodies to AQP4 in the cerebrospinal fluid of the patient at 22 years of age (red) compared with a healthy control individual (blue). Forward scatter on the x-axis indicates the size of the particles, and the total number of MPs is depicted on the y-axis. 8 Magnetic resonance imaging of the brain of our patient, showing inflammation (circled in red) of both optic nerves as they come together to form the optic chiasm structure. 9 Scanning electron microscopy (SEM) photograph of the very first four drops of cerebrospinal fluid, dropped directly on the polycarbonate filter, displaying a macrophage surrounded by numerous glycogen-like particles. 10 SEM photograph of the last four drops of cerebrospinal fluid shows a few spherical particles with a diameter of about 1 μm. 11 Photograph of cerebrospinal fluid from a healthy control individual does not reveal any specific particles. The diameter of the pores in the filter is 0.6 μm. Cartoons 1–6 are adapted with permission from Dutra BG, da Rocha AJ, Nunes RH, et al. Neuromyelitis optica spectrum disorders: spectrum of MR imaging findings and their differential diagnosis. Radiographics. 2018;38(1):169–93