Neuromyelitis Optica Spectrum Disorder (NMOSD)


The prevalence of neuromyelitis optica spectrum disorder (NMOSD) is between 0.5 and 4 per 100,000 people, although this number is higher in certain racial groups (up to 10/100,000). NMOSD has many phenotypic resemblances to multiple sclerosis (MS), and it was once considered a subtype of the disease before being recognized as its own entity following the discovery of aquaporin-4 (AQP4) antibodies.1 The prevalence of NMOSD is also distinct from that of MS, which affects mostly white individuals and increases with latitude.2 NMOSD affects black individuals more than white individuals, with a prevalence rate of 1.8 to 11.5 per 100,000 compared to 0.5 to 4.4 per 100,000.1 Geographic differences are noted with NMOSD, however, the association of increasing prevalence with increasing latitude is absent.

In East Asians, the prevalence of NMOSD is around 3.5 per 100,000, which is comparatively higher than that in other Asian populations. Chinese and Japanese populations share a common genetic risk factor, the HLA-DPB1*05:01 and HLA-DRB1*16:02 alleles, which supports the high prevalence rates in the region. Among South Indians in Mangalore, the prevalence is 0.72 per 100,000, and the prevalence is 1.09 per 100,000 in Arab countries.1 

In Latin America, the prevalence of NMOSD is between 1.3 and 2.2 per 100,000; however, data are scarce and may not be generalizable to the broader Latin American population. In the United States, prevalence rates vary between black and white individuals as described above. The rate in Mexican Mestizos is 1.3 per 100,000.1 

Clinical features and disability also vary between racial groups. Asian opticospinal MS (OSMS) is now considered to fall within the NMOSD spectrum. Prior to its designation as a member of NMOSD, it was considered a phenotype of MS upon the observation that MS presented differently in Asia than in North America and Europe. The main differences in Asian populations were a higher female to male ratio, more severe optic nerve and spinal cord involvement, fewer brain and cerebellar lesions, a higher proportion of optic nerve and spinal attacks, a lower proportion of progressive disease, and a lower incidence of positive oligoclonal bands.3 

Patients that present with NMOSD at a young age are more likely to present with optic neuritis as the initial presentation; meanwhile, an older age of onset is more likely to be associated with symptoms of myelitis. Age of onset also appears to have important prognostic implications since early onset optic neuritis carries a higher risk of eventual blindness than a later age of onset. Black individuals have a lower mean age of onset of 28 to 33 years compared to Asians and white individuals, with rates of 35 to 40 years and 44 years, respectively.  Furthermore, older patients experience more disabling disease with a prolonged recovery phase.1 

The likelihood of developing blindness and the severity of acute attacks are higher in black patients than in white and Japanese patients. On the other hand, motor disability is more pronounced in white patients than in Japanese patients. Black and Asian patients were more likely to have brain and brainstem attacks and abnormalities on brain magnetic resonance imaging (MRI) than white patients. The risk of relapse is lowest in Japanese patients.1 

NMOSD may be classified based on serologic markers into AQP4-positive and seronegative NMOSD. A subset of seronegative patients (7% to 42%) are positive for myelin oligodendrocyte glycoprotein (MOG) antibodies.1,4 Women are more affected by AQP4-positive disease than men, with a ratio of 9:1. Patients with MOG positivity have more optic nerve involvement than spinal cord involvement, and the male to female ratio is close to 1:1.1 Optic nerve involvement is more frequently bilateral and simultaneous in this group. Additionally, while a relapsing and remitting course may be present, it is frequently monophasic. Spinal cord lesions are usually distributed in the lower portion of the spinal cord and display better functional recovery following an attack.5 MOG-positive patients are also more likely to have brainstem involvement.6 The most frequent presentations of MOG-positive disease are acute disseminated encephalomyelitis in children under 7 years of age and optic neuritis in older children and adults.7  

References

1. Hor JY, Asgari N, Nakashima I, et al. Epidemiology of neuromyelitis optica spectrum disorder and its prevalence and incidence worldwide. Front Neurol. 2020;11:501. doi:10.3389/fneur.2020.00501

2. Simpson S Jr, Blizzard L, Otahal P, Van der Mei I, Taylor B. Latitude is significantly associated with the prevalence of multiple sclerosis: a meta-analysis. J Neurol Neurosurg Psychiatry. 2011;82(10):1132-1141. doi:10.1136/jnnp.2011.240432

3. Chong HT, Tan CT. A review of multiple sclerosis with Asian perspective. Med J Malaysia. 2008;63(5):356-361.

4. Kitley J, Woodhall M, Waters P, et al. Myelin-oligodendrocyte glycoprotein antibodies in adults with a neuromyelitis optica phenotype. Neurology. 2012;79(12):1273-1277. doi:10.1212/WNL.0b013e31826aac4e

5. Sato DK, Callegaro D, Lana-Peixoto MA, et al. Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders. Neurology. 2014;82(6):474-481. doi:10.1212/WNL.0000000000000101

6. Jurynczyk M, Messina S, Woodhall MR, et al. Clinical presentation and prognosis in MOG-antibody disease: a UK study. Brain. 2017;140(12):3128-3138. doi:10.1093/brain/awx276

7. 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

Reviewed by Debjyoti Talukdar, MD, on 10/18/2021.

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