Neuromyelitis Optica Spectrum Disorder (NMOSD)


Neuromyelitis optica spectrum disorder (NMOSD), previously known as Devic disease or neuromyelitis optica (NMO), is an inflammatory disorder affecting the central nervous system (CNS) in which immune-mediated axonal demyelination occurs predominantly in the optic nerves and spinal cord.1

A Separate Entity From Multiple Sclerosis

Originally considered a variant of multiple sclerosis (MS), NMOSD is now recognized as a distinct clinical entity with respect to pathogenesis, biomarkers, treatment, and prognosis.1

Compared with patients who have MS, those who have NMOSD are more likely to experience a severe clinical course and have their disease diagnosed at an older age.2

Most patients who meet the diagnostic criteria for NMOSD have a waxing and waning course in which repeated attacks are separated by periods of remission that may last weeks, months, or years.3

The prognosis of patients who have NMOSD is variable, with severe neurological disability a frequent development.4 

Relapsing Disease Versus Monophasic Disease

Most patients with NMOSD have a relapsing course, and their prognosis is poor in comparison with that of patients who have monophasic disease. Progressive disability is frequent in patients with relapsing NMOSD, as well as respiratory failure due to cervical myelitis.5

Patients with relapsing NMOSD are also likely to have recurrent attacks of optic neuritis and myelitis. These lead to severe neurologic sequelae and impairment, including blindness and paraplegia, within 5 years after symptom onset.

Predictors of severe disease and a poor prognosis include relatively frequent relapses within the first 2 years after onset, older age at onset, female sex, and a history of other autoimmune diseases.6

Mortality

Mortality rates in patients with NMOSD are high. Neurogenic respiratory failure secondary to the extension of primary lesions in the brainstem and cervical spine is the major cause of death.7

Overall mortality rates vary for patients with NMOSD. Some studies have estimated that mortality rates can range between 9% and 32%, depending on patients’ ages, rates of relapse, and rates of recovery from attacks. African American ancestry has been associated with a high mortality rate.8

In a Chinese retrospective study of 569 patients with 10 years of follow-up, the overall mortality rate was 4.2%, with a median duration of disease of 3.4 years at the time of death. The most common cause of death was respiratory infection, followed by respiratory failure secondary to cervical myelitis.9

Additional studies have found that if NMOSD is untreated, approximately 50% of patients will become blind and wheelchair-bound within 5 years. An additional one-third of patients with untreated NMOSD will die within 5 years after symptom onset.10

Biomarkers in Disease Prognosis

With improvements in antibody testing and the development of effective treatments, the risk for relapse has been reduced as a result of early detection of disease and treatment with immunosuppressive medications.11 

It has been suggested that the biomarker aquaporin-4 (AQP4) autoantibody NMO-IgG may have prognostic value in patients with NMOSD. Research has demonstrated an association between seropositivity and poor visual outcomes and the development of NMOSD.12

A separate prospective study of 594 patients with NMOSD found that individuals who were seronegative for AQP4-IgG had less severe clinical symptoms and a better overall prognosis, with lower disability rates than those of patients with NMOSD who were seropositive for AQP4-IgG.13

Pregnancy

Studies evaluating the relationship between pregnancy and NMOSD are limited but suggest that NMOSD is associated with an increased risk for miscarriage and that the risk for relapse is increased during the first 6 months post partum.14

References 

1. Glisson CC. Neuromyelitis optica spectrum disorder. UpToDate. Accessed October 29, 2021. 

2. Ghezzi A, Bergamaschi R, Martinelli V. Clinical characteristics, course and prognosis of relapsing Devic’s neuromyelitis optica. J Neurol. 2004;251(1):47-52. doi:10.1007/s00415-004-0271-0

3. Neuromyelitis optica spectrum disorder. National Organization for Rare Diseases (NORD). Accessed October 29, 2021. 

4. Neuromyelitis optica. EyeWiki. Reviewed October 13, 2021. Accessed October 29, 2021.

5. Wingerchuk DM, Hogancamp WF, O’Brien PC, Weinshenker BG. The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology. 1999;53(5):1107-1114. doi:10.1212/wnl.53.5.1107

6. Wingerchuk DM, Weinshenker BG. Neuromyelitis optica: clinical predictors of a relapsing course and survival. Neurology. 2003;60(5):848-853. doi:10.1212/01.wnl.0000049912.02954.2c

7. Zantah M, Coyle T, Datta D. Acute respiratory failure due to neuromyelitis optica treated successfully with plasmapheresis. Case Reports in Pulmonology. 2016. doi/10.1155/2016/1287690

8. Mealy MA, Kessler RA, Rimler Z, et al. Mortality in neuromyelitis optica is strongly associated with African ancestry. Neurol Neuroimmunol Neuroinflamm. 2018;5(4):e468. doi10.1212/NXI.0000000000000468

9. Du Q, Shi Z, Chen H. Mortality of neuromyelitis optica spectrum disorders in a Chinese population. Ann Clin Transl Neurol. 2021;8(7):1471-1479. doi:10.1002/acn3.51404

10. Huda S, Whittam D, Bhojak M, Chamberlain J, Noonan C, Jacob A. Neuromyelitis optica spectrum disorders. Clin Med (Lond). 2019;19(2):169-176. doi:10.7861/clinmedicine.19-2-169

11. NMOSD prognosis & management. Siegel Rare Neuroimmune Association. Accessed October 29, 2021.

12. Matiello M, Lennon VA, Jacob A, et al. NMO-IgG predicts the outcome of recurrent optic neuritis. Neurology. 2008;70(23):2197-2200. Doi:

13. Du Q, Shi Z, Chen H, et al. Comparison of clinical characteristics and prognoses in patients with different AQP4-Ab and MOG-Ab serostatus with neuromyelitis optica spectrum disorders. J Neuroimmunol. 2021;353:577494. doi:10.1016/j.jneuroim.2021.577494

14. Mao-Draayer Y, Thiel S,  Mills, E. Neuromyelitis optica spectrum disorders and pregnancy: therapeutic considerations. Nat Rev Neurol 2020;16:154-170. doi.org/10.1038/s41582-020-0313-y

Reviewed by Kyle Habet, MD, on 11/1/2021.

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