Possible causes and risk factors of multiple sclerosis
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The exact causes of multiple sclerosis (MS) are not known, but scientists have identified many risk factors that may contribute to MS development, including a person’s genetics, infection and disease history, demographic traits, and environment.MS is an autoimmune disease characterized by inflammation and damage to healthy parts of the central nervous system, composed of the brain and spinal cord.
What causes MS?
The immune system defends the body against foreign invaders, such as viruses and bacteria. Put simply, its job is to attack anything that could cause injury or disease, while leaving healthy tissue alone. In autoimmune diseases, however, the immune system erroneously recognizes certain cells or tissues in the body as a threat and launches an inflammatory attack against them.
In MS, the immune system attacks the myelin sheath, a fatty substance that wraps around nerve fibers. It normally protects the nerve fibers from damage and helps them send electrical signals efficiently — a bit like insulation wrapped around a metal wire. The loss of myelin leads to progressive nerve fiber degeneration and a range of MS symptoms.
Myelin is produced by cells called oligodendrocytes, found only in the central nervous system. These cells are normally able to remyelinate nerve cells — meaning wrap them in new myelin sheaths — but the repeated immune attacks against myelin lead to less and less effective remyelination and the eventual formation of scar-like MS lesions.
As is the case with most autoimmune diseases, scientists do not know what exactly causes MS, and multiple interconnecting factors likely contribute to disease development and progression. A number of factors, including an individual’s genetic makeup, history of infections or other autoimmune diseases, environmental exposures, and demographic traits, have all been linked with an altered risk of developing MS.
Genetic factors
MS is not a heritable disease, meaning that it is not passed from parents to their biological children. Nonetheless, a person’s genetic makeup profoundly affects MS risk, and about 1 in 5 patients have a history of the disease among their relatives.
Those with a parent with MS have a roughly 2% risk of developing the disease in their lifetimes. Similarly, having a child with MS also is associated with a 2% chance of developing the disease.
Notably, there’s a greater possibility of MS for those with a brother or sister with the disease: Having a sibling with MS is linked to an approximately 4% risk. If an identical twin has MS, there is a roughly 25% chance their twin also will develop the disease.
Adopted individuals are not at increased risk if those in their adoptive families have MS. Data suggest that genetics are mainly responsible for the differences in MS risk among families.
While the genetics governing MS risk are still not completely understood, some 200 genes are thought to possibly contribute — even in small ways — to MS development.
The strongest genetic risk factor is a particular variant of the HLA-DRB1 gene, called HLA-DRB1*15:01. This gene belongs to the human leukocyte antigen (HLA) family of genes, which help the immune system distinguish between infecting agents and the body’s own healthy tissues.
Variations affecting cellular receptors for immune signaling molecules, such as the receptors for interleukin-2 and interleukin-7, also have been strongly implicated in MS risk.
Infections and viruses
A history of infection with the Epstein-Barr virus, known as EBV, is one of the strongest risk factors for MS. In fact, EBV raises the risk of developing the autoimmune disorder by more than 30 times.
EBV infects most people at some point in their lives. It is mostly known for causing infectious mononucleosis — commonly known as mono — but its symptoms often are minor and escape notice.
The reason for this association is believed to be a structural similarity between certain EBV and brain proteins. That means that an immune response targeting the virus also can inadvertently attack healthy brain tissue, ultimately setting the stage for MS to develop.
Epstein-Barr is a member of the herpes virus family. Some other herpes viruses, including the varicella-zoster virus — which causes chickenpox and shingles — and human herpes virus 6 also have been linked to a higher risk of MS.
In addition to viral infections, other infections with bacteria also may increase MS risk, though these mechanisms are still not well understood.
Autoimmune diseases
In autoimmune disorders like MS, the immune system accidentally attacks its own healthy tissue. Many of these conditions share risk factors such as genetics, suggesting some common disease-driving mechanisms.
While specific associations and mechanisms are still being investigated, people with certain autoimmune diseases have an increased risk of developing MS. These diseases include the following:
| Type of autoimmune disease | Potential association |
|---|---|
| Type 1 diabetes | This autoimmune disorder affects the pancreas’ ability to produce insulin. It has been associated with a more than threefold higher risk of MS. |
| Inflammatory bowel diseases | Autoimmune conditions affecting the digestive system include ulcerative colitis and Crohn’s disease. Studies suggest that people with these conditions are 1.5 times more likely to develop MS. |
| Thyroid disorders | Graves’ disease and Hashimoto’s disease, conditions that respectively result in high and low levels of thyroid hormones, have been reported to be more common in MS patients than in the general population. |
| Pernicious anemia | This autoimmune disorder affects the production of red blood cells because not enough vitamin B12 is being absorbed. It also has been linked to heightened MS risk. |
| Psoriasis | Some studies have shown a link between MS and this autoimmune condition, which causes itchy, scaly skin. |
Environmental and lifestyle factors
Geography
The risk of MS varies geographically. In general, MS rates are lower in places nearer to the equator. Rates of the disease become increasingly higher as a person moves farther from the equator, according to research showing higher prevalence with greater degrees of latitude. MS, however, is a disease of temperate climates, being less common closer to the North and South poles.
Among people who move from one place to another, the relative risk of MS seems to vary depending on how much time the person spent living in places with higher or lower risk. Differences in sun exposure and vitamin D levels, as well as genetics and other variations, likely contribute to location-based differences in MS risk.
Vitamin D
Less exposure to sunlight is associated with an increased risk of developing MS. The mechanism of this association remains incompletely understood, but one important factor is thought to be a person’s level of vitamin D.
Vitamin D is a small molecule that is synthesized in the skin upon exposure to sunlight. Reduced sun exposure can lead to low vitamin D levels, which is an independent risk factor for MS.
This vitamin, also obtained from some foods and supplements, is important for maintaining bone health and modulating the activity of the immune system. It may protect from MS by blocking the production of immune cells and signaling molecules that drive the inflammatory response in MS.
Smoking
People who have ever smoked cigarettes are at a roughly 50% higher risk of developing MS than those who never smoked. A greater risk also was observed in passive smokers — people who breathe in others’ tobacco smoke — likely due to the toxins inhaled with the smoke. Smoking also is associated with a more severe disease course among those who develop the condition.
Obesity
Obesity — having a body mass index (BMI) higher than 30 — can lead to chronic inflammation in the body, which can help set the stage for the development of MS. People who are obese are roughly twice as likely to develop MS as compared with non-obese individuals.
Demographic factors
Age
MS can develop at any age, but most people with the disease first start experiencing symptoms in early adulthood. The majority of MS patients are diagnosed between ages 20 and 50. Notably, symptoms have been found to start several years prior to an MS diagnosis in some patients.
Sex
MS is about three times more common in females than in males. This disparity is thought to be driven mainly by differences in the levels of sex-related hormones — particularly estrogen in females and testosterone in males. These hormones can influence the activity of the immune system and how well the nervous system is able to repair damages.
Before the onset of puberty when hormone levels spike, MS rates are similar regardless of sex. Rates of MS later in life — after menopause/andropause and accompanying hormonal decreases — also are similar among the sexes.
Transgender women on hormone therapy, who are chromosomally XY but have “female” hormone profiles with high estrogen and low testosterone levels, have a comparably high risk of MS as cisgender women who have the same hormone profile with XX chromosomes.
Race and ethnicity
While MS can affect people of all racial and ethnic backgrounds, the disease is more common among certain groups of individuals. A number of interconnected factors, including genetics, climate, and socioeconomic disparities, likely contribute to these differences.
Although it was once believed that the risk of MS is relatively low among Black people, more recent research has shown that MS is actually more common in Black people than white people. On the other hand, MS risk is greater in white people, especially those of northern European descent, compared with individuals who are Latin American or Asian.
What are not MS risk factors?
Some factors, including at least one autoimmune disease, certain therapies, and consuming alcohol, have been shown to have no connection with the risk of developing MS.
- Statins are a class of medication used to lower cholesterol levels. Studies have shown that MS patients who are treated with statins generally experience similar clinical outcomes as patients who never receive statins.
- Radiation therapy, used to treat certain cancers, has shown no connection with the risk of developing MS. However, radiation to the brain may be more toxic to nerve cells in people who already have the disease.
- Lyme disease is a bacterial infection transmitted by certain ticks. Symptoms of Lyme disease, such as weakness or abnormal sensations, are often similar to those seen in MS, which can lead to diagnostic confusion. Like many infections, Lyme disease may serve as a trigger for MS relapses; however, there is no evidence that having Lyme disease increases the risk of developing MS.
- Guillain-Barre syndrome (GBS) is an autoimmune disease that affects the nervous system. Unlike MS, which affects the central nervous system (the brain and spinal cord), GBS affects the peripheral nervous system in the rest of the body. These two conditions may share symptoms and risk factors, but it is very uncommon for them to co-occur in the same person.
- Drinking alcohol does not increase the risk of developing MS. Some studies actually have suggested that people who drink alcohol may be less likely to develop MS, but this association remains unproven.
Potential MS risk factors for which more research is needed
For other potential risk factors, currently available research is contradictory as to whether there is a true connection to MS. It is possible that an association may either be confirmed or excluded with ongoing research.
- B12, also called cobalamin, is a vitamin necessary for maintaining the health of the myelin sheath. Some studies have shown a higher rate of B12 deficiency in MS patients, but other studies have found no connection between vitamin B12 deficiency and MS. There also is no evidence that B12 supplements benefit MS patients who have normal levels of the vitamin.
- Injuries to the head and spine — such as concussions from contact sports, or whiplash from a car accident — may increase the risk of developing MS later on, some studies have indicated. However, other studies have found no association between injuries and later MS risk, so at present no connection has been proven.
- Some research has shown a connection between stressful life events or childhood traumas and a higher risk of developing MS in the future; however, other studies have shown no such association. In people who already have MS, heightened stress may be a relapse trigger, and stress-management programs have been shown to reduce disease activity on MRI scans.
Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
FAQs about causes of MS
The strongest risk factor for multiple sclerosis known so far is infection with the Epstein-Barr virus (EBV). An EBV infection has been shown to increase the risk of developing the autoimmune disorder by 32 times. However, this infection alone is not enough to trigger the disease. Multiple interconnecting factors, including genetics, lifestyle, demographics, and environmental factors, all are thought to play a role in MS development.
Multiple sclerosis is an autoimmune disorder caused by a person’s immune system accidentally attacking that individual’s own healthy tissue. The disorder is not transmissible; it cannot be passed from one person to another.
Multiple sclerosis is more common in women than men, and the disease is mostly diagnosed in adulthood. White people are more often affected than Asians or Latin Americans, while rates of MS are higher among Black people than white people. MS is most common in temperate regions of the world that are further from the equator. People with certain genetic mutations or autoimmune diseases, as well as those who smoke or are obese, are also more likely to develop the condition.
No. The immune attack that drives multiple sclerosis is believed to broadly result from an immune system malfunction as immune cells fight off potential infections that are encountered throughout life. There have been reports of toddlers developing MS symptoms before age 2, but most children who develop the condition do so in their early teens.
The criteria used to diagnose multiple sclerosis require the presence of brain or spinal cord lesions on MRI scans that appear over time. Even if a person is found to have MS-like lesions at one point in time, there needs to be definitive evidence that lesions are developing over time for a formal diagnosis of MS to be made. Thus, by definition, it is not possible for MS to suddenly develop.
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