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My Mother’s Multiple Sclerosis Has Been a Life-Long Riddle; It May Soon Be Solved.


The mechanisms of MS are elusive, but new research into Epstein-Barr may finally shed some light.
EBV virus seen under an electron microscopic. Credit: CDC/ Dr. Fred Murphy
By Mark Kraus
Published March, 10, 2024.
“Years ago, they said it was from the measles.” My mother spoke about what led to her MS diagnosis, one that she kept hidden from us — my brother, sister, and I — for most of our lives. “When I was a kid, I nearly died...the doctor came in the middle of the night and they had to open up the pharmacy.” She recalled her own mother saying, “You became a different person...you had curly blonde hair, after that it was straight brown.” Enter the changeling, the doppelganger who raised me, and the suspected source of the affliction.

Scientists had once suspected a link between measles and MS, but new evidence points to another common virus. Researchers from Harvard have linked Epstein-Barr (EBV), a virus that lives in more than 90% of adults, with the onset of MS. The 20-year study found individuals who first tested positive for EBV were more likely to get MS, a correlation that could lead to a better understanding of the disease.

“MS was just very puzzling. It was intriguing to me. It feels almost sometimes like a riddle, people have been trying to understand it for ages.” I spoke by phone with Dr. Marianna Cortese, a lead researcher on the new study that links EBV and MS. “We think that MS may be a rare complication of EBV,” she said.


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We think that MS may be a rare complication of EBV.

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The study, which used data from military individuals who had their blood tested regularly, looked for commonalities in individuals who later went on to develop MS. Of the close to one thousand people who were later diagnosed with the disease, almost all had a prior EBV infection. “If you see the context...individuals who seroconverted with EBV — or got infected — have a 32-fold increased risk of developing MS compared to those that remained seronegative,” Dr. Cortese explained. No other virus showed an increased risk, including those viruses that are closely related to EBV, suggesting that it may be the primary cause of the disease.

Close to three million people worldwide are affected by MS, which turns the immune system against the body’s nerve cells and joints. Inflammation from this kind of attack produce “plaques,” opaque white areas that can be seen on MRI scans and signal the presence of the disease. These are legions in the brain, spine, neck, and back that are the result of nerve and tissue damage. Attacks are periodically triggered by stress in episodes called “flare-ups” that do damage throughout the nervous system that is often irreversible. The attacks can be debilitating, leaving some patients with a host of neurological issues.

My mom described the initial symptoms that led to get tested for MS as a strangeness in her body, which she initially ignored. “My sister said to me, ‘You’re just weird Eileen.’” Soon her feet stopped working as normal, “They were becoming like 20-lb weights.” By her early 50’s she explained, “Things I used to be able to do were becoming more difficult... I had a strange sensation in my arm, my hand was not working.”

After a few rounds of testing relating on her hand, her doctor shared what he thought would be unexpected news. At sixty-one years old she was diagnosed with MS. “I just went, well ok, I’m not all that surprised.” It was not the first time she received the diagnosis. When she was forty her neurologist said the same thing. At the time she admitted that she had some symptoms, but thought that because she wasn’t in a wheelchair, she didn’t have the disease. “My neurologist was crazy,” she concluded.

Speaking with Dr. Cortese, I could sense her excitement as she shared more about the mechanisms behind how EBV might cause the disease, like molecular mimicry. “It says that maybe the immune-response that we find against EBV happens to also target module structures...like human proteins.” It what might also be a zombie virus, where EBV affects the way memory B-cells act, causing them to attack the body and cause MS.

She admits more study is needed before we see breakthrough treatments, but there are already a few that may help shed more light. A recent paper published in the journal Nature may demostrate the molecular mimicry that Cortese described. And another paper may provide a way of recognizing an antibody signature in the blood, perhaps leading to an MS blood test.

For people like my mom, who have been able to keep the flare-ups at bay due to risky immune suppressing drugs, this research is welcome news. With perceptions of the disease have changing and new treatments on the horizon, there is a real sense of hope. Dr. Cortese is optimistic too. “The beauty is if we see that EBV is involved in the disease course, it could even mean we start dreaming of a cure. If you think further. It could be more than a treatment.”
1.
Kjetil Bjornevik, Marianna Cortese, Brian C. Healy, Jens Kuhle, Michael J. Mina, Yumei Leng, Stephen J. Elledge, David W. Niebuhr, Ann I. Scher, Kassandra L. Munger, and Alberto Ascherio. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis Science 13 Jan 2022 Vol 375, Issue 6578 pp. 296-301 https://www.science.org/doi/10.1126/science.abj8222
2.
What Causes MS? June 2023 nationalmssociety.org https://www.nationalmssociety.org/What-is-MS/What-Causes-MS/Viruses/legal>
3.
Lanz, T.V., Brewer, R.C., Ho, P.P. et al. Clonally expanded B cells in multiple sclerosis bind EBV EBNA1 and GlialCAM. Nature 603, 321–327 (2022). https://doi.org/10.1038/s41586-022-04432-7
4.
Dr. Marianna Cortese, personal Interview. 06/12/2023.
5.
Eileen Kraus. Personal Interview. 06/19/2023.
6.
Stork L, Ellenberger D, Ruprecht K, Reindl M, Beißbarth T, Friede T, Kümpfel T, Gerdes LA, Gloth M, Liman T, Paul F, Brück W, Metz I. Antibody signatures in patients with histopathologically defined multiple sclerosis patterns. Acta Neuropathol. 2020 Mar;139(3):547-564. doi: 10.1007/s00401-019-02120-x. Epub 2020 Jan 16.