What Causes Multiple Sclerosis?

Multiple sclerosis (MS) occurs when a person's immune system malfunctions and attacks healthy tissue within the central nervous system (CNS). The CNS consists of the brain, spinal cord, and optic nerves (nerves within the eyes).

The precise cause of MS remains a mystery. However, experts suspect the disease results from a combination of factors, namely a person's genetic makeup, faulty immune system, and exposure to various environmental factors.

This article reviews the immune system's role as well as genetic and environmental factors in MS manifestation. Strategies to help prevent MS, or at least slow down the disease if diagnosed, are also briefly explored.

Timeline of MS research milestones

Verywell / Joyce Chan

The Immune System and Multiple Sclerosis (MS)

A healthy immune system protects you from foreign, potentially harmful substances (e.g., viruses, bacteria, and toxins) entering the body and causing infection or disease.

In MS, cells within a person's immune system mistake myelin (the fatty sheath surrounding nerve fibers) in the CNS for a foreign substance and attack it.

Multiple Sclerosis

During these attacks, myelin is damaged and eventually destroyed (demyelination). The loss of myelin creates areas of inflammation (lesions) and scar tissue (sclerosis) in the CNS.

The lesions and scar tissue disrupt communication between the CNS and the rest of the body. From this disruption, various symptoms may develop, depending on the location of the inflammation in the CNS.

Common early warning signs of MS include vision problems and numbness/tingling. Other typical MS symptoms include fatigue, bladder problems, and muscle spasms.

Is MS an Autoimmune Disease?

Most experts consider MS an autoimmune disease because the immune system is causing the damage of healthy tissue. However, some experts prefer to call MS an immune-mediated condition because no specific MS antigens (proteins that can trigger the immune system) have been identified.

What Triggers MS?

The exact cause of MS, or why the immune system of some people (and not others) goes awry and attacks myelin, is unknown. That said, scientific studies support the theory that MS develops in people with specific genes exposed to one or more outside or environmental factors.

Besides genes and environmental exposures, other factors that affect MS development include:

  • Sex: MS is 3 times more common in females than males. This discrepancy may be explained by differences in sex hormones, namely estrogen.
  • Age: MS is typically detected between the ages of 20 and 40, although it can develop at any age. Pediatric MS accounts for 3% to 5% of MS cases. Late-onset MS (when symptoms develop after age 50) occurs in around 5% of cases.
  • Ethnicity: MS occurs in people of most ethnic backgrounds but is most often diagnosed among White people of northern European descent. 

Genetic Risk Factors for MS

MS is not a directly inherited disease, meaning it's not passed down predictably from generation to generation. However, some people are more likely to develop MS because of their genetic makeup.

The following statistical findings support the fact that genes play a role in developing MS:

  • In the general population, a person has an estimated 0.1% chance of developing MS.
  • MS risk increases to 2% if a person has a parent with MS and 5% if a person has a sibling with MS.
  • MS risk is at its highest—30%—if a person is an identical twin of someone with MS.

The idea that genes contribute to increased MS risk is further supported by a large study that analyzed the genetic makeup of over 47,000 people with MS. Study investigators discovered over 230 gene mutations (changes in DNA sequence) that influence MS risk.

Remember that inheriting one or more of these gene mutations is not sufficient alone to develop MS. Environmental factors must also be present to trigger disease onset.

Contributing Risk: Environmental Factors

A number of environmental factors influence the development of MS. In addition to infection with the Epstein-Barr virus (discussed later), environmental factors with the clearest supporting scientific evidence include the following.

Vitamin D Deficiency

Low levels of vitamin D are linked to an increased risk of developing MS. Vitamin D deficiency is also associated with a higher rate of MS activity.

Sources of Vitamin D

Vitamin D is produced naturally by the skin when exposed to the sun. It can also be obtained through supplements or foods like salmon, tuna, and vitamin D-fortified milk, orange juice, or ready-to-eat cereals.

Despite the strong association between vitamin D deficiency and MS, there is no consensus on how muc vitamin D is sufficient to prevent the disease. Likewise, in individuals with MS, more studies are needed to analyze how vitamin D supplementation (and what dose) could calm or slow the disease down.

If you have risk factors for MS—for example, a family history of MS—consider speaking with a healthcare provider about getting your vitamin D level checked.

Smoking

Smoking increases a person's risk of developing MS. In people already diagnosed with MS, smoking is linked to more significant disability, higher disease activity, and a faster rate of brain atrophy (shrinkage).

Experts suspect that cigarette smoke irritates the lungs, initiating an inflammatory cascade that may lead to MS development in genetically predisposed individuals. Also, toxic agents in cigarette smoke, like carbon monoxide or hydrogen cyanide, may directly harm nerve cells in the central nervous system.

The good news is that smoking cessation can help prevent MS and slow the disease down in those already diagnosed.

Obesity

Obesity, especially in early childhood and adolescence, increases the risk of developing MS. Moreover, in individuals already living with MS, obesity impacts the effectiveness of specific disease-modifying therapies.  

The link between obesity and MS has not been fully teased out, although inflammation is a common pathway between the two conditions. Excessive fat tissue (adipose tissue) in obesity creates a state of low-grade inflammation in the body.

Similarly, MS is a disease of inflammation, characterized initially by relapses (episodes of new or worsening neurological symptoms) and then neurodegeneration (dying of nerve cells) in the later stages.

If you have overweight or obesity, please speak with a healthcare provider about achieving a healthy weight, typically through regular exercise and a well-balanced diet.

Other Environmental Risk Factors

Other environmental factors that may contribute to an increased MS risk include:

  • Geography: MS is more common in people living in higher latitudes (areas of the world that are farther from the equator). Low sun exposure and subsequent lower vitamin D levels might explain this geographical risk of MS.
  • Gut health: Studies suggest a possible link between the gut microbiome (the organisms living in a person's digestive tract) and MS development. Diet, obesity, antibiotic use, and cigarette smoking all impact gut health.
  • Head trauma: Limited research has found that concussions in adolescence, especially multiple ones, are associated with an elevated risk of developing MS in the future.

Infectious Factors and MS

Many scientific studies suggest that infectious agents (e.g., viruses and bacteria) are the likely environmental insults that trigger MS in genetically susceptible young adults.

Infections with the following organisms have been associated with developing or worsening MS:

Is MS Contagious?

No, MS is not contagious. While specific viruses or bacteria may contribute to MS development or activity, MS is not a germ or infectious disease, so it cannot spread from one person to another.

Of all the infectious agents, Epstein-Barr virus (EBV) has perhaps the most robust evidence for contributing to MS development.

EBV, also known as human herpesvirus-4, is the most common cause of infectious mononucleosis (also referred to as mono), characterized by fever, extreme tiredness, sore throat, and swollen lymph nodes.

EBV spreads through body fluids, primarily saliva, and infects most people at some point in their lives, usually in childhood.

Research on EBV and MS has found that the severity of EBV infections is strongly linked with MS onset many years later. Specifically, experts believe that MS develops in genetically prone individuals when EBV-infected lymphocytes (cells in the immune system) seed the CNS and trigger an abnormal immune system response.

Can You Prevent MS?

Since the onset of MS involves several factors, including ones not in your control, like genetic makeup or ethnic background, there is no sure way to prevent the disease.

That said, adopting healthy lifestyle behaviors such as maintaining a healthy weight and stopping smoking may help prevent MS onset in genetically prone individuals.

Seeing a healthcare provider for regular checkups, blood tests, and vaccinations, such as COVID-19, is also key for helping avoid potential MS-triggering insults like infection or vitamin D deficiency.

If you have already been diagnosed with MS, you can optimize your care by taking your disease-modifying medicine as prescribed and seeing a treating physican for your MS who is up-to-date on the latest MS research.

Also, consider reaching out to an MS support group for connection, comfort, and healthy coping strategies as you navigate the ebbs and flows of this unpredictable disease.

Summary

The exact cause of MS has yet to be fully understood. Although, research suggests the disease results from the complex interplay of genetic factors and exposure to environmental factors, namely infectious agents (e.g., Epstein-Barr virus), vitamin D deficiency, smoking, and obesity. Non-modifiable factors like age, sex assigned at birth, and ethnic background also contribute to MS risk.

It's impossible to predict who or why some people will develop MS and others will not. However, practicing lifestyle behaviors such as avoiding smoking, maintaining a healthy body weight, and visiting a healthcare provider for regular checkups may help prevent the disease or slow its course if already diagnosed.

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Colleen Doherty, MD

By Colleen Doherty, MD
 Colleen Doherty, MD, is a board-certified internist living with multiple sclerosis.