Neuromyelitis Optica Spectrum Disorder (NMOSD)


Neuromyelitis optica spectrum disorder (NMOSD) is a chronic, relapsing, and autoimmune disorder of the central nervous system characterized by inflammation of the optic nerve and spinal cord. Patients with NMOSD typically suffer recurrent attacks of optic neuritis and transverse myelitis.1,2

Mortality in NMOSD

The mortality associated with NMOSD is high and variable. When it is not identified or when it remains untreated, about 30% of patients die within the first 5 years of the disease.3 About 50% of patients become blind a wheelchair-bound when left untreated.4 Death in patients with NMOSD typically occurs due to respiratory failure.5 

Previous reports have suggested a 22% to 30% 5-year mortality rate.6 Other studies estimate a 9% to 32% mortality rate for NMOSD worldwide.7 Improvements observed in the treatment and therapeutics for NMOSD are expected to contribute to a decrease in mortality, with suggested mortality rates as low as 3% to 7%.6 A different study shows a mortality rate of 4.2%, with 3.4 years as the mean duration of the disease until death. The most common cause of death reported in this study was secondary infection.8

Life expectancy depends on several factors, such as the patient’s age, type of disease, frequency, and recovery from relapses.7 

Factors Affecting Life Expectancy in NMOSD

Patients who have a relapsing course of NMOSD show a higher risk of developing recurrent attacks of optic neuritis and transverse myelitis.9 A recent study on relapse patterns showed that optic neuritis may occur more frequently in patients less than 30 years of age, while transverse myelitis often occurs later in life.10

The median time to the first relapse is 8.5 to 14 months. How well patients recover from relapses can impact mortality rates.7 A previous study reported that 83% and 67% of patients experiencing transverse myelitis and optic neuritis attacks, respectively, do not recover or only partially recover.11 Additionally, the recurrence of these attacks leads to an accumulation of neurological disability, which significantly impacts the development of long-term visual and motor disabilities. About 25% of long-term disabilities are related to the initial onset attack.12 The attacks reduce life expectancy when they affect the brainstem or cause damage to the medulla, increasing the risk of respiratory failure.13 The risk of disability-related mortality appears to be higher when patients have aquaporin-4 (AQP4) antibodies in the serum.12

NMOSD has been reported in all ethnicities, however, incidence and prevalence are higher in non-white patients.2 A recent study revealed a higher mortality rate in patients with African ancestry.7 The disease more commonly affects women, with a male to female ratio of 1:9 to 1:10 when patients are AQP4-seropositive. The median ages of disease onset were reported to be 40 years in AQP4-immunoglobulin (Ig) G-seropositive patients and 31 years in myelin oligodendrocyte glycoprotein (MOG)-IgG-seropositive patients. A late onset, observed in patients over 50 years of age, is associated with increased motor disability and potentially higher mortality rates.2

Impact of NMOSD Treatment on Life Expectancy

In patients with NMOSD, the chance of recurrence within 5 years is greater than 90%.11 Early diagnosis and treatment in NMOSD may help improve the prognosis of the disease. Studies have shown that patients who endure optical and severe spinal events at the first attack have a better clinical outcome when treated earlier.4,14 A preventive treatment with immunosuppressive therapies, such as eculizumab, satralizumab, or inebilizumab monoclonal antibodies, may therefore help reduce the risk of recurrence and induce remission, which may ultimately impact disability and death.4,11,13 

References

1. Neuromyelitis optica spectrum disorder. National Organization for Rare Disorders. Accessed November 1, 2021.

2. Jarius S, Paul F, Weinshenker BG, Levy M, Kim HJ, Wildemann B. Neuromyelitis optica. Nat Rev Dis Primers. 2020;6(1):85. doi:10.1038/s41572-020-0214-9

3. Neuromyelitis optica spectrum disorder. Orphanet. Updated November 1, 2021. Accessed November 2, 2021.

4. 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

5. Zantah M, Coyle TB, Datta D. Acute respiratory failure due to neuromyelitis optica treated successfully with plasmapheresis. Case Rep Pulmonol. 2016;2016:1287690. doi:10.1155/2016/1287690

6. Wallach AI, Tremblay M, Kister I. Advances in the treatment of neuromyelitis optica spectrum disorder. Neurol Clin. 2021;39(1):35-49. doi:10.1016/j.ncl.2020.09.003

7. 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. doi:10.1212/NXI.0000000000000468

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

9. 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

10. Khalilidehkordi E, Clarke L, Arnett S, et al. Relapse patterns in NMOSD: evidence for earlier occurrence of optic neuritis and possible seasonal variation. Front Neurol. 2020;11:537. doi:10.3389/fneur.2020.00537

11. Brod SA. Review of approved NMO therapies based on mechanism of action, efficacy and long-term effects. Mult Scler Relat Disord. 2020;46:102538. doi:10.1016/j.msard.2020.102538

12. Palace J, Lin DY, Zeng D, et al. Outcome prediction models in AQP4-IgG positive neuromyelitis optica spectrum disorders. Brain. 2019;142(5):1310-1323. doi:10.1093/brain/awz054

13. Contentti EC, Lopez PA, Pettinicchi JP, et al. Assessing attacks and treatment response rates among adult patients with NMOSD and MOGAD: data from a nationwide registry in Argentina. Mult Scler J Exp Transl Clin. 2021;7(3):20552173211032334. doi:10.1177/20552173211032334

14. Drulovic J, Martinovic V, Basuroski ID, et al. Long-term outcome and prognosis in patients with neuromyelitis optica spectrum disorder from Serbia. Mult Scler Relat Disord. 2019;36:101413. doi:10.1016/j.msard.2019.101413

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

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

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