The incidence of multiple sclerosis (MS) is rising worldwide, but scientists are not in agreement as to why. MS carries with it a profound disease burden, often impacting people at stages of life in which they are busy building careers and planning families. Therefore, it is imperative that we understand what contributes to someone developing this disease, either immediately or over a period of time, so appropriate intervention can be introduced early.
In this article, we will be looking at a study conducted by Walton and colleagues that charted the rise in the prevalence of MS worldwide and exploring a theory by Xu et al concerning a possible association between being hospital-diagnosed with an infection before the age of 20 years and the subsequent risk of developing MS.
A Rising Global Concern
Walton and colleagues track the prevalence of MS through “The Atlas of MS,” an open-source global aggregation of data on the epidemiology of the disease. The Atlas of MS documents MS prevalence at national, regional, and global levels.
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The Atlas of MS serves a very important purpose in helping us understand MS: it allows for the large-scale collection of epidemiological data for a disease that is already poorly understood in terms of etiology and treatment.
The last time the Atlas of MS was updated was in 2013. The latest effort to collect data between 2019 and 2020 would allow scientists to track MS epidemiological changes after a roughly 7-year period.
“Country representatives reported epidemiologic data and their sources via survey between September 2019 and March 2020, covering prevalence and incidence in males, females and children, and age and MS type at diagnosis,” wrote Walton et al.
Through this latest update to the Atlas of MS, Walton and colleagues reported a number of notable findings:
- The estimated global number of patients with MS was 2.8 million in 2020, a rise of 30% from 2013.
- This increase has been noted in most world regions; only 14% of countries reported stable or declining prevalence.
- In 2013, 7000 cases of pediatric-onset MS were reported; in 2000, that number had risen to 30,000.
- Females are consistently more likely to have MS than males.
Walton and colleagues did not go into detail in discussing the reason for such a large difference in data between 2013 and 2020. However, they emphasized that projects like the Atlas of MS provide physicians with vital data that can be used to argue for further funding and targeted research.
“We call on policy makers, health professionals, and MS organizations to use Atlas of MS data to stimulate additional research, raise awareness of MS, and support evidence-based advocacy efforts,” Walton et al wrote.
Infection and the Risk of MS
Now we turn our attention to a fascinating study conducted by Xu and colleagues on the possible association between hospital-diagnosed infections before age 20 and the risk of a subsequent MS diagnosis.
For some time now, MS researchers have noted an association between viral infection in adolescence and an increased risk of MS later in life. However, they have largely explained this away by infectious mononucleosis.
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Xu et al argued that the body of literature discussing the increased risk of MS with previous infection, especially the Epstein-Barr Virus, human herpesvirus 6, and Chlamydia pneumoniae, deserves a closer look. They thus identified the patient group they wanted to study through the Swedish National Patient Register: people who had a hospital-diagnosed infection before the age of 20 and who developed MS after the age of 20.
“Any hospital-treated infections in adolescence rather than in earlier childhood increased the risk of a multiple sclerosis diagnosis from age 20 years, though the effect size was small (HR:1.33) as not all types of infection are associated with a subsequent multiple sclerosis diagnosis (possibly other unmeasured characteristics of infections, such as severity/duration or repeated exposure, may also be important),” wrote Xu and colleagues on their key finding in their study.
What could possibly explain this association? Xu and colleagues suggested that infection could have possibly damaged the central nervous system (CNS) by triggering autoimmune processes that are relevant in the pathogenesis of MS. This theory is further validated by reports that CNS infection is associated with a greater risk of developing MS, compared to viral, bacterial, or respiratory infection.
“Inflammation in the CNS caused by autoreactive T cells due to possible molecular mimicry between the infectious pathogens and an individual’s myelin antigens may be another possible mechanism,” wrote Xu et al. In this theory, antibodies cross-react with myelin antigens to cause CNS autoimmune damage.
Walton et al, through their work with the Atlas of MS, and Xu et al, through their work on the association between adolescent infection and the increasing risk of MS, both show a commitment to adding to the body of data regarding MS so that we can move forward in our goal to better prevent, and treat, MS. Through their work, we have a better understanding that MS is a living disease (in the sense that its prevalence changes and that it is receptive to external stimuli in its pathogenesis) and that we will undoubtedly learn more about it with continued research.
References
Walton C, King R, Rechtman L, et al. Rising prevalence of multiple sclerosis worldwide: insights from the Atlas of MS, third edition. Mult Scler. Published online December 26, 2020. doi:10.1177/1352458520970841
Xu Y, Smith KA, Hiyoshi A, Piehl F, Olsson T, Montgomery S. Hospital-diagnosed infections before age 20 and risk of a subsequent multiple sclerosis diagnosis. Brain. Published online March 9, 2021. doi:10.1093/brain/awab100
