Re-thinking race and geography in multiple sclerosis

Multiple sclerosis (MS) has traditionally been viewed as predominantly affecting White people from North America or Europe. ¹ Indeed, a significant proportion of research involving people with MS has been based in Europe or North America. As a result, the epidemiology of MS is heavily influenced by how MS presents in White populations from these regions. Inaccurate inferences have been made that race is a decisive variable in who gets MS. However, it is now clear that MS is a global disease that affects all racial and ethnic groups, albeit with some geographic variability. MS diagnosis may be heavily influenced by economic stability in the region and health care access. ² The globalization trends seen in the last 50 years challenge us to rethink race and geography in MS.

In a recent publication, conducted under the auspices of the National Multiple Sclerosis Society, researchers identified evidence of increasing prevalence of MS in the United States among underrepresented minorities and by sex for 2008 and 2010. ³ They found that women continue to be disproportionately affected as compared with men and significantly that the prevalence of MS in Hispanic and Black populations is increasing concomitant to an increase in non-Hispanic Whites. The study is among the first to comprehensively assess MS in underrepresented populations nationally. The results are important because they reaffirm prior observations that MS is not an uncommon disease in Black and Hispanic populations. ⁴ In addition, it underscores the need for further research specific to populations categorized under the “other” category which included individuals who identified as Asian or Pacific Islander or Native Hawaiian, Native American or Alaska Native, and multiracial. Third, the geographical differences of lower prevalence in the southern regions of the United States are also areas of growing racial and ethnic diversity, which in many cases have less access to neurologists. Hidden health disparities and inequities are likely to exacerbate over the future. The Hispanic population is the fastest growing population (18.7%—a 23% growth from 2010) and as a multiracial population has seen tremendous growth also after 2010 (276% increase between 2010 and 2020). ⁵ The Black and African American population has also grown (12.1% increase) which also highlights that these prevalence estimates may be far from the truth today. ⁵

Race and ethnicity are not biological constructs and in medicine and countries like the United States are entangled with racial injustices that have led to disproportionate higher morbidity and mortality in minorities. MS is more severe in both presentation and clinical course in Hispanic and Black American people. ⁶ The exact underpinnings of these differences are not clear, but several studies suggest greater lesion volume and specific topologies may explain the more severe clinical phenotype observed.^7,8 Increased spinal cord lesions have been shown in Hispanic populations, ⁹ and in Black populations, greater structural loss in the spinal cord has also been described. ¹⁰ Differences between Hispanic American people born in the United States and those who migrated during either childhood or adult life have been shown to be different ¹¹ with later age of migration associated with increased disability accrual. Clinical trials in MS do not always report on race and ethnicity and when they do, it is clear the majority of participants are White. ¹² Whether other racial and ethnic groups differ in relation to treatment outcomes is not definitively known, but some subgroup analyses have shown poorer response in African Americans ¹³ and Hispanics. ¹⁴ However, access to neurological care also may be poor for minorities based on social and geographic reasons compounding biological differences. ¹⁵ A major underlying question, however, is whether the differences observed are a product of biological/genetic factors or the result of social determinants of health and access to care. In this sense, complementing studies with genetic markers could serve as better proxies of biological assessments across individuals in specific circumstances. ¹⁶ The advent of our ability to genotype large cohorts of MS patients may provide the ideal scenario to differentiate possible genetic and social differences that may drive clinical outcomes.

Finally, perhaps one of the most significant problems not only of MS, but of health sciences in general, is how we should move forward with the categorization of race and ethnicity. Race and ethnicity are self-ascribed or assigned, while genetic ancestry is not. The issues are quite complex, particularly among Hispanic Americans who are not a monolithic group and may self-identify as Black, White, Asian, or multiracial. Hispanic ancestry is a genetic admixture of mainly Native American/American Indian, European, and African ancestries ¹⁷ with differing proportions as a consequence of complex political, social, and migratory histories to regions. Genetic admixture differences within African American and Hispanic populations have been found to correlate with an individual’s risk of MS. ¹⁸ This highlights a central role for the inclusion of ancestry to complement future examinations where both global and local variant-specific ancestral risk modifications could influence prevalence or phenotypic differences across racial and ethnic groups. Several ongoing clinical trials that focus on underrepresented populations build on this observational data complementing race and ethnic self-identify with genetic data. ¹⁹

The realization that MS is prevalent in racial and ethnic unrepresented populations and that health disparities and health inequities are present in MS should lead us to rethink race in MS. The guidance for reporting on race and ethnicity is an intentional action that has the capacity to decrease structural racism and achieve greater racial equity in the future and should be followed. ²⁰ Hence, future studies should detail how race and ethnicity are categorized and acquired (self-report or census-based, etc.). Careful attention to socioeconomic factors, access to care, and factors that derive from racial stratification (biases, racism, and discrimination) should take place that are pertinent to the geographical area of study. Avoidance of generalizations from a broader category of population to represent another by keeping in mind the limitations of population identifiers should be considered. For example, researchers should not generalize the “other non-Hispanic” category to represent all multiracial people. In addition to the integration of language and reporting, methodological advancements that integrate ancestry analyses of diverse populations and a re-evaluation of existing methodologies to assess race are necessary. By attending to these issues, we are more likely to elucidate the factors behind variations in prevalence, incidence, and outcomes of MS within diverse racial and ethnic groups. Global, national, or regional mandates may be needed. Forthcoming efforts that mandate reporting of MS cases tagged with social demographics including race and ethnicity in the state of California ²¹ are likely to provoke thought just as has done for Puerto Rico. ²²

In summary, underrepresented populations represent a growing proportion of patients with MS in clinical practice. This proportion will only increase as the US transitions to a time where White is no longer a majority of the population, which is expected to occur by 2045. Health care providers and researchers need both the tools and knowledge to be able to care for individuals of different ethnic and racial backgrounds. Clinical trials will need to enroll a greater number of minority patients, and we will need to proactively design research to better understand MS across all patients and across all geographical regions.