Multiple sclerosis is a big deal in Canada. Our country has one of the highest rates of the disease worldwide, with聽聽having received the diagnosis. To put this into perspective, imagine Montreal鈥檚 Olympic Stadium, which seats 56,040 people. If you fill the stadium with a representative sample of our country鈥檚 population, you will find roughly 163 people with multiple sclerosis seated there.
Anyone afflicted by a health condition knows that putting a name to it offers some amount of solace. Likewise, figuring out what聽肠补耻蝉别诲听it can relieve us of mental anguish over what we might have done or failed to do that led us here.
For a long time, medical researchers suspected that multiple sclerosis was caused by a virus, and this focus on infection was narrowed down to one specific viral bad boy: the Epstein-Barr virus (EBV). As of 2022, we know that EBV is a necessary but insufficient cause of the disease.
Yet, how do we explain that most of us carry the virus but will never develop multiple sclerosis?
Present at the scene of the crime
To explain what happens with multiple sclerosis, we often talk about electrical wires. They have a plastic insulation wrapped around them, and our nerve cells have a similar sheath called myelin. When the immune system attacks this sheath in people with the disease, the conduction of information from one nerve cell to another slows down or stops completely. This results in symptoms like numbness, tingling, weakness, vision loss, pain, vertigo, and fatigue.
Its constellation of symptoms was first recognized as a distinct disease by the famous French neurologist Jean-Martin Charcot in 1868, and a student of his, Pierre Marie,聽聽that this聽scl茅rose en plaques, as it was called, might be caused by an infection.
In modern times, a number of viruses have been implicated in multiple sclerosis. But it鈥檚 the Epstein-Barr virus that, up until recently, was the prime suspect, yet to be properly condemned by a scientific judge. This virus is primarily transmitted via saliva. Given children鈥檚 propensity for sticking things in their mouth, it鈥檚 no surprise that most of us first make contact with EBV as kids. And usually, we鈥檙e fine. But when our close encounter happens in our teens or early twenties instead, the virus can give us what we commonly call 鈥渕ono.鈥澛�
Infectious mononucleosis results in a sore throat, fever, and swollen glands, and it is typically caused by EBV, although other agents like cytomegalovirus can be responsible. EBV thrives in the cells lining the inside of our mouth and throat, but once it is done causing havoc, it doesn鈥檛 go away. Like a bear digging its den for hibernation, the Epstein-Barr virus moves somewhere else to lie dormant, specifically our blood鈥檚 B cells, which are part of the immune system. The virus鈥� DNA forms a circle and stays deep inside these B cells, waiting to be awakened.
While EBV is often unjustly fingered by the wellness industry as the cause of just about any symptom in the worried-well (see my article about this聽here), it has been a legitimate suspect in the world of multiple sclerosis for decades, and there are good reasons for that. If you had mono in the past, your risk of developing multiple sclerosis is聽鈥攊t goes up by a factor of 2.3, to be exact, and it鈥檚 important to keep in mind that the baseline risk is already quite low. The more antibodies you have in your blood against specific proteins in the virus, 聽of getting diagnosed with multiple sclerosis. Also, when the nerve cells stripped of their insulation are looked at by a pathologist,聽聽they find the Epstein-Barr virus in those lesions.
None of this is proof that EBV聽肠补耻蝉别蝉听multiple sclerosis. The way to prove it would be to purposely infect a cohort of people with the virus and see if they are more likely to develop multiple sclerosis than a cohort shielded from the virus, and I hope that we don鈥檛 need to be ethicists to realize that such a study should not be conducted. Instead, what we can ethically do is to follow a large-enough cohort of people who has not been exposed to the virus; see who naturally ends up infected and who doesn鈥檛; and follow both groups long enough to see if the group exposed to the virus has many more cases of multiple sclerosis than the one who never got infected.
The problem is, how do you find this large group of individuals who gets regular blood draws starting at a young age and who can be followed for decades?
The answer: the U.S. military.
A 32-fold increase
When joining the U.S. Armed Forces, blood is drawn to test for HIV, and further blood tests are conducted every other year. Once the tests are run, there is a leftover, which is archived. This is what a team at Harvard University tapped into to look at the over 10 million members of the Armed Forces who were on active duty between 1993 and 2013.
Among this monumental cohort, the researchers identified 955 military personnel who were eventually diagnosed with multiple sclerosis, with 801 having enough blood samples available for this research project. They were matched to other members who were similar to them in terms of age, sex, ethnicity, branch of military service, and the dates when they got their blood drawn but, importantly,聽who were never diagnosed with multiple sclerosis. So now, you have personnel with the disease and very similar personnel without the disease. Archived blood samples were tested for the presence of antibodies against the Epstein-Barr virus.
The result was staggering. Testing positive for antibodies against the Epstein-Barr virus鈥攎eaning that they had been exposed to the virus鈥攑ut military personnel at a聽32-fold increased risk聽of developing multiple sclerosis. In fact, out of the 801 members with multiple sclerosis, 800 of them tested positive for EBV exposure in the last available blood sample. The odd person out had their last blood draw a year before multiple sclerosis started manifesting itself, so it鈥檚 possible they became infected in that 12-month period; it鈥檚 also possible they were misdiagnosed, or that they failed to seroconvert, meaning that they were exposed to the virus but failed to or stopped making antibodies against it鈥攑ossibly because their immune system was compromised in some way. That鈥檚 one person out of 801 who tested negative for the virus in the multiple sclerosis group; by comparison, 46 out of 1,566 in the non-multiple-sclerosis group tested negative for the virus in the last sample tested.
The resulting聽聽from this study, which was published in聽厂肠颈别苍肠别听in 2022, has been downloaded nearly half a million times, and it鈥檚 fair to say that it sealed the deal as far as the Epstein-Barr virus鈥� culpability is concerned, especially since its authors looked at antibodies against any other viral infection and saw no difference between the two groups鈥� except for the Epstein-Barr virus.
It鈥檚 not just present at the scene of the crime; it鈥檚 holding the knife. But just like in a good mystery novel, there are a few wrinkles to keep the reader guessing.
Somewhere between聽聽of the population has been infected by the Epstein-Barr virus, and yet most of us do not have multiple sclerosis. One聽聽put it best, I think, by calling multiple sclerosis 鈥渁 rare complication of a ubiquitous virus.鈥� We may think this situation is singular but it鈥檚 not uncommon. That same virus can cause cancer: in fact, it was聽迟丑别听very first virus shown to cause cancer in humans, being identified as the guilty party in a type of blood cancer called pediatric Burkitt lymphoma. But again, most of us have the virus, yet it only 肠补耻蝉别蝉听聽of cancer in humans. Human papillomaviruses (HPV) are another example. They are聽聽and most infections result in zero symptom鈥� except that some go on to develop cancer because of them.
翱迟丑别谤听聽enter the multiple sclerosis equation, like accomplices to the head honcho. Smoking increases the risk of developing multiple sclerosis, as does being chronically exposed to cigarette smoke, to organic solvents, and to air pollution. Obesity in adolescence and early adulthood also doubles the risk for multiple sclerosis, presumably by creating low-grade inflammation. Over 200 variations in the human genome have been tied to multiple sclerosis, and many of them are in genes that code for proteins that play a role in the immune system. The disease is twice as common in women as in men, an observation that applies to many conditions in which the immune system starts attacking the body. Finally, sun exposure and vitamin D levels have been implicated: the further from the equator you live, the greater the risk. Less sun exposure can mean lower levels of vitamin D in the body (although our food supply is supplemented with vitamin D), and these lower levels are also associated with multiple sclerosis.
But by far, the most important risk factor is infection by the Epstein-Barr virus, which won鈥檛 mean much to the average person. How do you avoid the virus, especially given that most of us have it and we鈥檙e fine?
People obsessed with their health and physical performance, like athletes and dancers, have been diagnosed with multiple sclerosis. Receiving the diagnosis is not a marker of failure as a human being. It鈥檚 the complex and still unpredictable dance of a body dealing with the presence of a very specific virus. A popular theory, backed up by evidence, is that the antibodies our body produces to fight off the Epstein-Barr virus can also start attacking parts of our nervous system, but the conditions have to be just right鈥攐r just wrong鈥攆or this to happen.
Knowing that the Epstein-Barr virus lies at the centre of the multiple sclerosis web keeps the door open for more preventative and therapeutic approaches focusing on the virus. Developing a vaccine against EBV seems like a logical move, and experimental vaccines have been tested in the past. Unfortunately, the virus is sneaky, despite not having a brain. It spreads very easily and persists in the body, and it may not be possible to fully prevent an infection by the virus with a vaccine but merely to delay it. And delaying this infection would be harmful.
Being exposed to the virus as a child is usually fine; being exposed to it as a teenager invites mono, and having mono increases our chances of developing multiple sclerosis. A deficient vaccine could backfire, so researchers need to be careful. Antivirals against EBV鈥攎eaning molecules that prevent the virus from functioning or from making more copies of itself鈥攈ave also been tested in the past and will continue to be developed in the hope of finding some that are both safe and effective.
Biology is lamentably complicated. We can exclaim an 鈥渁h-HA!鈥� when we finally catch the Epstein-Barr virus after trawling through 10 million U.S. Armed Forces records鈥� and yet still find ourselves unable to fully explain how we go from being infected to developing multiple sclerosis. This is why, when our Office scrutinizes pseudoscience, we often remark that pseudoscience hangs on a gross oversimplification of the world around us. Biology, chemistry, physics鈥攊t鈥檚 rarely black-and-white. Studying our universe reveals shades of grey we didn鈥檛 even know existed.
Take-home message:
- Multiple sclerosis is a rare complication from an Epstein-Barr virus infection
- 90 to 95% of the population has been infected by the virus. When we catch it as a child, it usually does not make us sick, but when we catch it as a teenager or a young adult, it often leads to mono
- It appears as if our immune system鈥檚 response to the virus can, in rare cases, get turned against our nervous system, leading to multiple sclerosis
- Other risk factors for multiple sclerosis include smoking, being obese as a teenager or young adult, living far from the equator, being a woman, and having one or many of a large number of specific variations in your DNA
