AUTHOR: Michael Z. Moore, MD
Neuromyelitis optica spectrum disorder (NMOSD) is an uncommon autoimmune inflammatory demyelination disorder of the central nervous system (CNS). It is a clinical syndrome defined by predilection to affect particular regions of the CNS: Specifically the optic nerve, spinal cord (typically with longitudinally extensive transverse myelitis), and some areas of the brain including periependymal regions (most strikingly the area postrema). The clinical syndrome is further subdivided into seropositive NMOSD (AQP4-IgG+ - 80% of patients) and seronegative NMOSD (MOG-IgG+, negative for both AQP4-IgG and MOG-IgG, or unknown serologic status).1
Though presently not well understood, there has been postulated a genetic predisposition towards NMOSD. Specifically relevant to seropositive NMOSD, associations with AQP4-IgG seropositivity and HLA-DRB1∗03 (DR3) in French and Brazilian populations and HLA-DPB1∗0501 in Japanese and Chinese populations have been described.6
Findings depend on the location of the CNS lesion(s) and may include the following:
As AQP4 is expressed in the central nervous system most abundantly on the foot processes of astrocytes, seropositive NMOSD should be understood as an antibody-mediated astrocytopathy. In a clinical relapse, accumulation of AQP4-IgG stimulates an inflammatory response mediated by such factors as complement activation and interleukins such as interleukin-6 (IL-6), leading to the influx of granulocytes. This cascades into a substantial local inflammatory response, leading to bystander damage of local cells and cell products such as myelin or axons themselves. On the other hand, MOG-IgG associated NMOSD is more clearly demyelinating, with some histopathologic studies bearing features similar to type II MS pattern demyelinating lesions.6 The specifics of non-MOG-IgG seronegative NMOSD pathophysiology are less well understood.
NMOSD remains a clinical diagnosis, supported by serologic studies for the antibodies and/or characteristic MRI findings (Box 1).
BOX 1 2015 International Consensus Diagnostic Criteria for NMOSD
Magnetic resonance imaging (MRI) of the brain and spinal cord with and without contrast is recommended in all cases. There are some imaging patterns to recognize in NMOSD:
Patient education regarding disease characteristics, treatment options, risks and benefits of treatment, and prognosis. Often, patients need to incorporate intermittent rest periods on a daily basis and when physically active (for energy conservation), and avoid exposure to heat, which typically worsens symptoms (but not the disease).
Recommend physical therapy for new or worsening weakness, incoordination, or spasticity.
TABLE 1 Drugs With Phase II/III Trials in NMOSD
Drugs with Phase II/III Trials in NMOSD | |||
---|---|---|---|
Name | Mechanism of Action | Dose and Delivery | Side Effects/Monitoring |
Eculizumab10 | Inhibits the terminal complement protein C5 and prevents its cleavage into C5a, which is pro-inflammatory, and C5b, which coordinates the formation of membrane cytolytic attack complex. | 900 mg intravenously weekly for the first 4 doses starting on day 1, followed by 1200 mg every 2 weeks starting at week 4 | -Approved for AQP4-IgG positive NMOSD -Increased infections with leukopenia and lymphopenia -Increased risk of infection with encapsulated bacteria, especially Neisseria meningitidis (meningococcal vaccination is mandatory before starting treatment) |
Inebilizumab11 | Binds to the B-cell surface antigen CD19 targeting B cells and CD19+ plasmablasts | 300 mg administered intravenously on days 1 and 15 every 6 months | -Approved for AQP4-IgG positive NMOSD -Lymphopenia, reduced immunoglobulin levels -Increased infections |
Satralizumab12-13 | Binds to membrane-bound and soluble IL-6 receptors, preventing IL-6 from binding and inhibiting the IL-6 signaling pathways involved in inflammation | 120 mg subcutaneously at weeks 0, 2, and 4 and every 4 weeks thereafter | -Approved for AQP4-IgG positive NMOSD -Leukopenia, increased infections |
Rituximab9 | Binds to the B-cell surface antigen CD20 surface expressed on B-lymphocytes | 375 mg/m2 intravenously every week for 4 weeks, then 6-month interval dosing (alternatively, 2 doses of 1,000 mg with 2 weeks interval) | Extralabel use for NMOSD |
Adapted from Mora Cuervo DL et al: Immunobiology of neuromyelitis optica spectrum disorders, Curr Opin Neurobiol 76(102618):102618, 2022. Table 1.
Multiple organizations exist to spread awareness, fund research, and support patients with NMOSD. Among these are the Siegel Rare Neuroimmune Association (https://wearesrna.org/), the Sumaira Foundation (https://www.sumairafoundation.org/), and the Guthy-Jackson Charitable Foundation (https://guthyjacksonfoundation.org/).
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