Neuromyelitis optica spectrum disorder (NMOSD) was once thought to be one and the same as multiple sclerosis, given that so many signs and symptoms between these 2 conditions overlap. However, the discovery in 2005 that roughly 8 in 10 cases of NMOSD is associated with aquaporin-4 antibodies (AQP4-Ab) meant that clinicians could reliably distinguish NMOSD as a separate disorder from multiple sclerosis.
It is fair to say that NMOSD is a relatively new disorder in the sense that it has only recently been clinically defined, and even that has not received universal assent. Epidemiologists studying the prevalence of NMOSD have arrived at different figures regarding how common this disorder is; if we are to use the 2015 criteria (requiring 1 out of 6 clinical features and AQP4-Ab positivity or 2 specific clinical features in AQP4-Ab seronegative patients), scientists estimate that the prevalence of this condition is approximately 0.7-10/100,000 persons across the globe.
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In Current Opinion in Ophthalmology, Holroyd and colleagues presented a number of key features that set NMOSD apart from other demyelinating disorders. For example, they reported that the prevalence of NMOSD is higher among individuals of Asian and African descent compared to those with European ancestry. NMOSD also has a higher prevalence in women compared to men, roughly in a 9:1 ratio.
It remains less clear how NMOSD is spread out geographically, and whether geographical factors play a role in influencing manifestations of the disease. Perhaps the most important factor attached to geography is access to diagnostic tools capable of testing for AQP4-Ab, without which actual figures can be artificially depressed.
Scientists also remain less clear about whether environmental factors influence the risk of developing NMOSD. Some of the usual suspects come into play — low physical activity, an unbalanced diet, and smoking. Also, many patients with NMOSD have other autoimmune disorders, such as myasthenia gravis and Sjorgen’s syndrome. Clustering of NMOSD has also been observed within families.
NMOSD and Medical Imaging
Magnetic resonance imaging (MRI) is an excellent imaging tool for diagnosing NMOSD and assessing the extent of clinical damage. Studies reveal that as many as 50% of patients with NMOSD have nonspecific T2 white matter lesions; more than 30% also meet the McDonald criteria for multiple sclerosis.
“Typical MRI lesion patterns seen in NMOSD include long corticospinal tract lesions (>3 or more contiguous vertebral segments), diencephalon and dorsal brainstem lesions adjacent to the third and fourth ventricles (specifically in the area postrema of the medulla), longitudinally extensively enhancing optic nerve lesions, and deep white matter lesions in the brain,” Holroyd and colleagues wrote.
Imaging evidence of optic neuritis is also characteristic of NMOSD. Many patients with NMOSD have either bilateral optic neuritis or some posterior involvement of the optic chiasm and tracts. Patients with multiple sclerosis may also present with optic neuritis, but they differ from individuals with NMOSD in that they tend to have recurrent optic neuritis episodes affecting the same eye; they are also at a greater risk of having widespread demyelination in the posterior visual pathways compared to individuals with NMOSD.
Further Differentiating Between NMOSD and Multiple Sclerosis
On the subject of medical imaging, Cortese and colleagues conducted a study in which they assessed whether imaging characteristics can be used to differentiate NMOSD from myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and relapsing-remitting multiple sclerosis (RRMS).
As mentioned, MRI is an excellent imaging tool for diagnosing NMOSD and other demyelinating disorders. The medical literature is rich with descriptions of how imaging features differ between various demyelinating disorders in the brain, spinal cord, and optic nerve. As such, Cortese and colleagues sought to investigate if MRI was sufficiently sensitive to differentiate between NMOSD, MOGAD, and RRMS, without the inclusion of optic nerve imaging.
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Adult patients with either of these 3 disorders were recruited for the trial. They then underwent comprehensive MRI scans and had their disability status assessed using various functional scores, such as the Expanded Disability Status Scale. The research team was explicit in their goals: identifying differences in the brain, cervical cord, and optic nerve between these 3 diseases, as well as any imaging markers that can be used to reliably discriminated between them.
The scope of this study and its findings are expansive, but 3 main conclusions could be derived from the observations made. First, the number of brain cortical and white matter lesions can be used to differentiate RRMS from the other 2 demyelinating disorders. Second, the magnetization transfer ratio of the optic nerve is of significant importance in differentiating between RRMS and NMOSD. Third, NMOSD and MOGAD share many imaging similarities, with the main point of differentiation being the presence of at least 1 cervical cord lesion in NMOSD.
In light of these reports, it is important to acknowledge that, while demyelinating diseases may share many similarities, we have sufficient information to properly distinguish between them based on imaging characteristics alone. This illustrates the progress that has been made from just a few decades ago, when imaging differences were poorly characterized.
Writing about the significance of their findings, Cortese and colleagues wrote, “When, especially outside the acute phase, serologic testing is unavailable or ambiguous, or a false-negative serologic result is suspected, these [imaging] markers can be of value to support the differential diagnosis.”
References
Holroyd KB, Manzano GS, Levy M. Update on neuromyelitis optica spectrum disorder. Curr Opin Ophthalmol. Published online November 1, 2021. doi:10.1097/ICU.0000000000000703
Cortese R, Prados Carrasco F, Tur C, et al. Differentiating multiple sclerosis from AQP4-neuromyelitis optica spectrum disorder and MOG-antibody disease with imaging. Neurology. Published online January 17, 2023. doi:10.1212/WNL.0000000000201465
