What Causes Multiple Sclerosis?

A chronic disease that affects the central nervous system, multiple sclerosis (MS) interrupts the flow of information both within the brain and between the brain and other parts of the body. Significant strides have been made in the last couple of decades in understanding the mechanisms of MS and types of treatment that can slow progression. What’s not fully known: the definitive cause of the disease.

Recent research has provided clues, suggesting that a combination of genetic susceptibility, viral infections, and environmental factors contribute to the development of multiple sclerosis, according to Misbah Azeem, M.D., a neurologist who specializes in treating MS at National Jewish Health in Denver, CO.

“For now, our priority is early identification of people presenting with symptoms that do not yet fit the criteria for having MS but are at high risk to develop it in the future,” he says. “When we see that, appropriate treatment can significantly reduce the risk of future relapses.”

What Happens in the Body to Cause Multiple Sclerosis?

The brain and spinal cord form the central nervous system, which controls movement, sensation, vision, thinking, and a breadth of other essential functions. Nerve cells in this system communicate by sending electrical signals along long extensions called nerve fibers.

These fibers are surrounded by a protective substance called myelin. Similar to insulation around an electrical wire, myelin helps protect the nerve fibers so signals can travel quickly and efficiently.

“In multiple sclerosis, inflammation damages myelin and can also injure the nerve fibers themselves,” says Vijayshree Yadav, MBBS, a neurologist and professor of neurology at the Oregon Health & Science University in Portland, OR. “The damaged areas may develop scar tissue, which is where the term multiple sclerosis—which means many scars—comes from. Everything we do is controlled by the central nervous system, so when nerve signals are disrupted, it can lead to a range of effects.”

She explains that symptoms of multiple sclerosis can include:

• Bladder or bowel difficulties
• Blurred or double vision, or eye pain
• Difficulty walking, being coordinated, or maintaining balance
• Emotional issues, including depression and anxiety
• Fatigue and problems with concentration or memory
• Muscle weakness and spasticity
• Numbness and tingling

Symptoms vary depending on which areas of the nervous system are affected and how much damage occurs, says Dr. Yadav. It’s also possible to have MS with no symptoms at all, particularly in the early stages of the condition.

Is Multiple Sclerosis an Autoimmune Disease?

Although multiple sclerosis is widely classified as an autoimmune disease, it doesn’t fit into the same category as others with that designation such as lupus, rheumatoid arthritis, or Graves’ disease. “MS occurs because of a dysfunction within the body’s immune system, but there’s no identifiable autoantibody, which is commonly seen in other autoimmune diseases,” says Dr. Azeem. “Because of that, it’s more appropriate to call MS an immune-mediated disease.”

Is Multiple Sclerosis Hereditary?

While MS can run in families, it’s not directly inherited in the way some other genetic disorders may be, according to Amy Laitinen, M.D., a neurologist and director of multiple sclerosis and neuroimmunology at Marcus Neuroscience Institute, part of Baptist Health South Florida in Boca Raton.

“There is a genetic component—over 200 genes are associated with the risk of developing MS and there is also a gene related to developing severe MS,” Dr. Laitinen says. “However, genetics alone are not sufficient as a cause. The estimated risk of developing multiple sclerosis in a first-degree family member is approximately 4%.”

By comparison, in other genetic conditions such as Huntington’s disease, if one parent has it, each child has a 50% chance of developing the condition. The low correlation for MS means genetic testing cannot reliably predict whether an otherwise healthy person will develop the condition. As such, family history is considered a risk factor but not a guarantee of future illness, Dr. Laitinen notes.

Does Epstein-Barr Virus Cause Multiple Sclerosis?

In the past decade, Epstein-Barr virus (EBV) has emerged as one of the strongest known risk factors for MS and may play a critical role in its development, says Dr. Yadav. Epstein-Barr is a common virus best known as the cause of infectious mononucleosis, often called mono. Many people infected with EBV are asymptomatic and do not even know they have the virus.

Research has found a significant relationship between EBV infection and MS. One analysis of 20 years of health data from more than 10 million young adults in the U.S. military found that the risk of developing multiple sclerosis rose 32-fold after an individual had EBV.

There isn’t a clear reason for this connection, but Dr. Yadav says theories are being investigated, including one major theory that certain immune cells produce antibodies that recognize both EBV proteins and certain proteins in the nervous system and see them as the same thing. That may be leading the immune system to attack healthy tissue by mistake.

“It’s important to recognize that having EBV doesn’t mean you will inevitably develop MS,” says Dr. Yadav. “The vast majority of people infected with EBV won’t develop the disease, but it’s a factor worth noting when you’re trying to determine potential causes.”

Environmental and Lifestyle Risk Factors for MS

In addition to some genetic links and exposure to viral infections, researchers have identified several environmental and lifestyle factors associated with increased risk of multiple sclerosis.

Low Vitamin D and Limited Sun Exposure

Vitamin D helps regulate immune system activity, and research has found strong associations between low levels of the vitamin and higher risk of developing MS. Some (inconsistent) research also suggests that low vitamin D can increase the chances of MS relapse. Before you head to the drugstore to stock up, though, know that no evidence suggests taking vitamin D supplements can prevent MS.

Smoking and Secondhand Smoke

Smoking is a well-established, modifiable risk factor for multiple sclerosis, says Dr. Azeem. Research suggests that people who smoke have a higher likelihood of developing MS compared to those who have never smoked, and smoking is associated with more aggressive disease progression in people who already have MS, he adds.

The connection likely comes from chemicals in tobacco smoke that promote inflammation and may affect immune function, Dr. Azeem explains. When combined with genetic susceptibility and other environmental factors, smoking may be a “trigger” for MS development.

Obesity During Childhood or Adolescence

Increasingly, research suggests that excess body fat affects how the immune system develops and operates, says Dr. Yadav. Studies have linked obesity during childhood and adolescence with an increased risk of developing MS later in life.

“The connection with obesity may be more profound if it’s combined with other factors like smoking and low vitamin D,” she adds.

Who Is More Likely to Develop Multiple Sclerosis?

Although MS can affect people of any background, certain factors associated with development of the condition mean some people may be at greater risk of multiple sclerosis than others. These include:

• Family members. Having a parent, sibling, or other close relative with MS increases risk, although as noted, the increase is small. Certain inherited genetic variations also affect immune system function and increase susceptibility.
• People who had mono. Infection with EBV is strongly associated with MS development.
• People who were overweight as kids. Obesity during childhood or adolescence is associated with increased risk.
• People living in extreme northern or southern locations. MS is more common in areas farthest from the equator. This may be because limited sunlight exposure contributes to low vitamin D, which has been linked to greater susceptibility.
• Smokers. Tobacco use increases risk and is also associated with worse disease outcomes.
• Women. Women are more likely than men to develop MS, particularly the relapsing-remitting form of the disease.
• Younger adults. Multiple sclerosis is frequently diagnosed in young adulthood, often between ages 20 and 40, although it can begin later in life as well.

Despite the statistical odds that put these groups at greater risk of multiple sclerosis, Dr. Yadav notes that many people with multiple risk factors won’t develop the disease, while others with no obvious risk factors may be diagnosed with MS.

Can Multiple Sclerosis Be Prevented?

Currently, there is no proven way to prevent MS. And even though scientists have found a correlation between certain risk factors and the disease, the removal of these factors does not appear to alter the odds of multiple sclerosis development. For example, completely avoiding smoking and secondhand smoke or getting adequate vitamin D has not been shown to lower cases of multiple sclerosis significantly, says Dr. Azeem.

“That means you can be doing everything ‘right’ with staying healthy and still develop MS,” he adds. “We just don’t know yet what can be done to prevent the disease. The research remains interesting and ongoing.”