Neuromyelitis optica spectrum disorders: still evolving and broadening

Abstract

Purpose of review: The diagnostic criteria of neuromyelitis optica spectrum disorders (NMOSD) has been revised in the past 20 years and pathological and therapeutic data have been accumulated. This review provides an overview of evolution and broadening of the concept of NMOSD.

Recent findings: NMOSD encompassing brain syndrome as well as optic neuritis and acute myelitis is now classified into aquaporine-4 (AQP)-antibody-seropositive and aquaporine-4 (AQP)-antibody-seronegative diseases, detecting more patients earlier than before. Seronegative NMOSD includes cases of myelin oligodendrocyte glycoprotein (MOG)-antibody-seropositive disease with its unique clinical spectrum somewhat different from AQP4-antibody-seropositive NMOSD. Pathologically, NMOSD includes AQP4-antibody-seropositive autoimmune astrocytopathic disease and MOG-antibody-seropositive inflammatory demyelinating disease. Double seronegative group needs further research. Therapeutic options of NMOSD has taken shape and first-ever clinical trials of monoclonal antibodies have been done. In retrospect, relapsing NMO in the studies preceding the discovery of AQP4-antibody had features of AQP4-antibody-seropositive NMO whereas monophasic NMO was similar to AQP4-antibody-seronegative/MOG-antibody-seropositive NMO.

Summary: The clinical, pathological and therapeutic concepts of NMOSD have evolved and broadened over the last two decades following the detection of AQP4 antibodies and MOG antibodies in the patients. Double seronegative NMOSD is a current research focus, but now we may need to reconsider how NMOSD should be defined.

Box 1

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FIGURE 1

History of the diagnostic criteria of neuromyelitis optica and neuromyelitis optica spectrum disorders: evolution and broadening of the clinical concept. Devic's NMO case and other early reports of the disease were published since late 19th century. Then, in the last two decades, the diagnostic criteria of NMO and NMOSD have changed. Absolute required clinical manifestations are shown in bold letters. The clinical concept has evolved and broadened from NMO (1999 and 2006) to NMOSD (2007 and 2015), and from ON and MY with no other CNS Disease (1999) to ON and MY (2006) to NMO or ON or LETM (2007) to One Core Clinical Characteristic (ON or MY or Brain Syn) in AQP4-antibody-seropositive NMOSD and two or more core clinical characteristics (one of them should be ON or MY or APS) in AQP4-antibody-seronegative NMOSD (or serostatus unknown) (2015). With these changes, NMOSD can be diagnosed earlier in a wider range of patients. APS, area-postrema syndrome; AQP4-Ab, aquaporin 4-antibody; CNS, central nervous system; LETM, longitudinally extensive transverse myelitis; MY, acute myelitis; NMO, neuromyelitis optica; NMOSD, neuromyelitis optica spectrum disorders; ON, optic neuritis; Syn, syndrome; VS, vertebral segments.