Neuromyelitis optica (NMO) is an autoimmune disease of water channels that predominantly damages astrocytes, specific cells in the brain. The injured astrocytes in turn cause secondary damage to myelin—the insulating sheath around nerve fibers. Hence, NMO and its spectrum disorders (NMOSD) are considered inflammatory demyelinating diseases (IDDs). Aquaporin-4–immunoglobulin G (AQP4-IgG) is the specific biomarker for NMOSD and most accurately diagnosed using a cell-based blood test. According to a multi-collaborative, population-based study on the epidemiology of NMOSD led by Mayo Clinic, an estimated 16,000 to 17,000 people in the U.S. are afflicted by the disease, especially among the black population.
Study findings, published in Annals of Neurology, emphasize the need for clinicians to use newer cell-based assays rather than older generation non-cell-based tests, which are less reliable.
“When you’re using older generation techniques such as the ELISA, for example, there is a higher risk of false positives,” says Eoin Flanagan, M.B., B.Ch., Mayo neurologist and first author on the study paper. “And when you do a population-based seroprevalence study where you’re testing hundreds of people—some of whom are less likely to have NMO—it is important to use the very best test available with the lowest possible risk for false positives. The cell-based assay for testing Aquaporin-4–IgG that we used in this study is a very, very good test. It’s 99% to 100% specific, which means there are very few false positives.”
The study is the first of its kind to compare NMO/NMOSD seroepidemiology (using AQP4-IgG seroprevalence assessment) across two ethnically divergent populations with IDD diagnosis: Olmsted County, Minnesota (predominantly white Caucasians), and Martinique, French West Indies (predominantly Afro-Caribbeans).
Findings confirmed that the Afro-Caribbeans were about 2.5 times more predisposed to NMO/NMOSD than the Caucasians: The age- and sex-adjusted prevalence rate (as of December 2011) among blacks in Martinique was 10 per 100,000, the highest reported thus far of any population, versus a prevalence of 3.9 per 100,000 in Olmsted County.
Unlike prior such studies that were not able to take blood samples, the Mayo-led study took blood from 80% to 85% of patients. “That was a real benefit of this study, that we were able to sample all of these patients and determine who had NMO,” says Dr. Flanagan.
While results determined that blacks are disproportionately affected, the reasons behind it cannot be completely understood without further studies.
“We found a similar prevalence among the black community in Olmsted County as what it was in Martinique,” says Dr. Flanagan. “And in Martinique, we found a similar prevalence in whites as we did in Olmsted County. What this suggests is that prevalence is related to your ethnicity. So if you’re black, you’re at higher risk for NMO/NMOSD. We’re suspicious that the reason may be that blacks are more genetically disposed to this disease, but we weren’t able to analyze that in our study.”
NMO causes very similar symptoms to multiple sclerosis (MS), which also damages myelin, and the two can be confused with one another. However, MS is more common worldwide. MS is particularly frequent in regions furthest from the equator and was thus more prevalent in Olmsted County than Martinique.
“We showed that if individuals from Olmsted County presented with symptoms of damage to myelin, such as optic neuritis, they were fifty times more likely to have MS than NMO,” says Dr. Flanagan. “However, if they were from Martinique and presented in this way, they were only three to four times more likely to have MS.”
Thus, when determining the baseline risk of NMO in a population, it is important for clinicians to take into account the ethnicity and distance from the equator, as both are important factors in determining the risk of NMO.
Early diagnosis and access to treatment are paramount, especially given that a single NMOSD attack can be severe enough to render a patient permanently blind or paraplegic—the spinal cord, optic nerve, and the area postrema (the vomiting and nausea control center of the brain) are particularly affected. As blacks in the U.S. tend to have less access to—and lower quality of—health care, they are particularly vulnerable to the effects of this disease because they may not receive timely, acute treatment or have the resources to receive treatments to prevent attacks and, as such, may experience a worse outcome.
Dr. Flanagan also hopes these study findings will encourage the development of public health strategies to improve access and quality of health care for the black population afflicted with NMO. “For allocation of resources and health care delivery, it’s important that we know these patients are more predisposed to this disease,” he says. “And I think that’s a major advance in this study because we’ve shown it for the first time.”