Materiały źródłowe

• #1 Multiple Sclerosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK499849/

  Although the exact etiology of multiple sclerosis is unknown, factors involved in pathogenesis are broadly grouped into 3 categories immune factors, environmental factors, and genetic associations. […] Dysimmunity with an autoimmune attack on the CNS is the leading hypothesized etiology of multiple sclerosis. The postulated „outside-in” mechanism involves CD4+ proinflammatory T cells among various proposed mechanisms. […] Environmental factors, such as latitudinal gradients observed in various countries, have been extensively studied. […] Vitamin D deficiency has been considered a possible etiology for the noted predisposition of populations in higher latitudes to multiple sclerosis. […] Patients with biological relatives with multiple sclerosis have a heightened risk of developing the condition. […] The human leukocyte antigen (HLA) DRB1*1501 allele strongly correlates with multiple sclerosis and is one of the most studied alleles relative to multiple sclerosis linkage. […] Polymorphisms in several genes may be associated with a slightly increased risk of multiple sclerosis.

• #1 Multiple Sclerosis (MS): What It Is, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/17248-multiple-sclerosis

  Multiple sclerosis (MS) is an autoimmune condition that affects your brain and spinal cord (central nervous system). […] With MS, your immune system mistakenly attacks myelin cells. These are the protective covers (sheaths) that surround your brain and spinal cord nerves. Myelin sheath damage interrupts messages (signals) that your nerves send throughout your body to perform functions like vision, sensation and movement. […] Demyelination, or the destruction of myelin, causes multiple sclerosis. Myelin is a protective cover (sheath) around nerve cells (neurons) in your brain and spinal cord. It moves messages (signals) between your brain and the rest of your body to control functions like vision, sensation and movement. […] Your immune systems job is to protect your body from things that can harm it, like bacteria or viruses. With MS, your immune system becomes overactive and mistakes healthy myelin (and sometimes, the nerve cells below the myelin) as a threat to your body. Your immune systems attack on the healthy myelin damages it. This is demyelination.

• #1 Multiple sclerosis – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/multiple-sclerosis/symptoms-causes/syc-20350269

  We don’t know what causes MS, but there are certain factors that may increase the risk or trigger its onset. […] The cause of multiple sclerosis is not known. It’s considered an immune-mediated disease in which the body’s immune system attacks its own tissues. In MS, the immune system attacks and destroys the fatty substance that coats and protects nerve fibers in the brain and spinal cord. This fatty substance is called myelin. […] It isn’t clear why MS develops in some people and not others. A combination of genetics and environmental factors may increase the risk of MS. […] Factors that increase the risk of multiple sclerosis include: Age. MS can happen at any age. However, onset most commonly happens between 20 and 40 years of age. […] Women are 2 to 3 times more likely than men to have relapsing-remitting MS.

• #1

  https://journals.lww.com/md-journal/fulltext/2024/02230/review_of_multiple_sclerosis__epidemiology,.15.aspx

  Multiple sclerosis (MS) emergence is a perplexing matter; its origins remain a mystery. However, newer investigations infer that it arises from a fusion of genetic vulnerability and environmental agents from development to young adulthood. Specific factors deemed highly culpable in regard to genetic disposition for MS and ability to make an impact include a lack of vitamin D, birth season, tobacco use, and exposure to Epstein-Barr virus.[7,8] […] In MS, cytokine-producing T cells with a preference for myelin are frequently immunogenic, resulting in Th1-like proinflammatory responses. Myelin destruction in MS appears to be primarily initiated by T-helper cells (cluster of differentiation 4 [CD4]+). In particular, autoreactive CD4+cells, particularly the Th1 variant, appear to be the main culprits and are likely activated after viral infection in the periphery.

• #1 Multiple sclerosis – Wikipedia

  https://en.wikipedia.org/wiki/Multiple_sclerosis

  MS is not considered a hereditary disease, but several genetic variations have been shown to increase its risk. Some of these genes appear to have higher expression levels in microglial cells than expected by chance. The probability of developing MS is higher in relatives of an affected person, with a greater risk among those more closely related. An identical twin of an affected individual has a 30% chance of developing MS, 5% for a nonidentical twin, 2.5% for a sibling, and an even lower chance for a half-sibling. If both parents are affected, the risk in their children is 10 times that of the general population. MS is also more common in some ethnic groups than others. […] The prevalence of MS from a geographic standpoint resembles a gradient, with it being more common in people who live farther from the equator (e.g., those who live in northern regions of the world), although exceptions exist. The cause of this geographical pattern is not clear, although exposure to ultraviolet B (UVB) radiation and vitamin D levels may be a possible explanation. For example, those who live in northern regions of the world have less exposure to UVB radiation and lower levels of vitamin D, and a higher risk for developing MS. Inversely, those who live in areas of higher sun exposure and increased UVB radiation have a decreased risk of developing MS.

• #1 Multiple sclerosis – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/multiple-sclerosis/symptoms-causes/syc-20350269

  If one of your parents or siblings has had MS, you are at higher risk of developing the disease. […] A variety of viruses have been linked to MS, including Epstein-Barr. Epstein-Barr is the virus that causes infectious mononucleosis. […] People with white skin, particularly those of Northern European descent, have the highest risk of developing MS. […] MS is far more common in places with temperate climates. These include Canada, the northern United States, New Zealand, southeastern Australia and Europe. […] Having low levels of vitamin D and low exposure to sunlight is linked to a greater risk of MS. […] People who are obese or were obese in childhood have an increased risk of multiple sclerosis. […] You have a slightly higher risk of developing MS if you have other autoimmune conditions. These may include thyroid disease, pernicious anemia, psoriasis, type 1 diabetes or inflammatory bowel disease. […] People who smoke have a higher risk of relapsing-remitting MS than people who don’t smoke.

• #1 Unravelling the causes of MS – MS Australia

  https://www.msaustralia.org.au/unravelling-the-causes-of-ms/

  Risk factors are anything or any exposure that increases the likelihood of developing MS, but they are not the direct or only cause of MS. […] MS is not considered a classical genetic disease in that there is not one single gene that causes MS. Rather, there are over 110 different known genetic factors which contribute to MS. It has been estimated that genetics may account for around half of the risk of MS, and those with a family history of MS are at greater risk than the general population. Even so, the majority of people with a family member with MS will not develop the disease so genes on their own are not enough. […] Most of these 110+ genetic factors, each only contribute a very small part of the risk of MS, although one immune system gene, known as HLA-DRB15*01 is known to contribute a much larger part of the genetic risk. This gene is also more commonly found in people of northern European ancestry, which also partially explains why these populations are more likely to develop MS than people with other ethnic backgrounds.

• #1 Primary Progressive Multiple Sclerosis (PPMS): Symptoms

  https://my.clevelandclinic.org/health/diseases/14202-primary-progressive-multiple-sclerosis-ppms

• #1 What Causes Multiple Sclerosis (MS)? | National MS SocietyNational Multiple Sclerosis Society LogoNational Multiple Sclerosis Society LogoOpen search

  https://www.nationalmssociety.org/understanding-ms/what-is-ms/what-causes-ms

  Scientists do not know for certain what causes multiple sclerosis. They believe that a mix of factors trigger MS. Studies support the idea that a trigger in the environment may cause MS in certain people who have a specific combination of genes. […] Research also suggests that ethnicity and geographic location play a role. To identify the cause of MS, research is focusing on: Immunology – the study of the body’s immune system, Epidemiology – the study of disease patterns in large groups of people, Genetics – understanding the genes that may not be functioning correctly in people who develop MS, Infectious agents – viruses that may contribute to developing MS. […] Although the cause of MS is not known, we are learning more about environmental factors that contribute to the risk of developing MS. No single risk factor provokes MS. Researchers believe that several factors contribute to the overall risk.

• #1 Possible Causes of Multiple Sclerosis | MSAA

  https://mymsaa.org/ms-information/overview/possible-causes/

  Some scientists are looking for a connection between MS and nutritional factors, including fat intake, as well as deficiencies in fish oil and vitamin D. The idea that a diet rich in saturated fat may increase ones risk of getting MS, as well as worsen his or her disease course, has been a popular theory for several decades. […] In addition to food and supplements, vitamin D is also derived from sunlight, which may be involved in the development of MS. As noted in the section, Who Gets MS, populations living closer to the equator experience a lower incidence of MS. A popular theory is that those living closer to the equator are exposed to more sunlight and therefore are less likely to experience a vitamin D deficiency (studies suggest that low levels of vitamin D may increase ones risk of MS).

• #1 Primary Progressive Multiple Sclerosis (PPMS): Symptoms

  https://my.clevelandclinic.org/health/diseases/14202-primary-progressive-multiple-sclerosis-ppms

  The exact cause of MS is unknown. Research suggests it could be related to changes in your DNA (genetic predisposition) that make you more likely to have an autoimmune condition. Genetics only play a small part in MS, so your risk of passing the condition onto your future children is low. […] Environmental factors can also play a role in developing MS. An example is exposure to bacteria or viruses. […] If you have MS, your immune system mistakenly attacks healthy parts of your central nervous system, which causes symptoms.

• #1 Multiple sclerosis – Wikipedia

  https://en.wikipedia.org/wiki/Multiple_sclerosis

  Early evidence suggested the association between several viruses with human demyelinating encephalomyelitis, and the occurrence of demyelination in animals caused by some viral infections. One such virus, Epstein-Barr virus (EBV), can cause infectious mononucleosis and infects about 95% of adults, though only a small proportion of those infected later develop MS. A study of more than 10 million US military members compared 801 people who developed MS to 1,566 matched controls who did not. The study found a 32-fold increased risk of MS development following EBV infection. It did not find an increased risk after infection with other viruses, including the similar cytomegalovirus. These findings strongly suggest that EBV plays a role in MS onset, although EBV alone may be insufficient to cause it.

• #1 The Probable Infectious Origin of Multiple Sclerosis

  https://www.mdpi.com/2673-4087/4/3/19

  Among the environmental factors that have been implicated in the development of MS are infectious agents and microbes. […] The role of infectious agents is also supported by the “hygiene hypothesis,” which proposes that reduced exposure to pathogens early in life can increase the risk for autoimmune diseases like MS. […] Numerous infectious agents have been suggested to play roles in the pathogenesis of MS, including viruses, bacteria, and parasites. Among the most widely studied are Epstein–Barr virus (EBV), human herpesvirus 6 (HHV-6), varicella-zoster virus (VZV), Chlamydia pneumoniae, and Helicobacter pylori; however, to date, no infectious agents have been proven to cause MS.

• #1 Possible Causes of Multiple Sclerosis | MSAA

  https://mymsaa.org/ms-information/overview/possible-causes/

  Also noted in the section, Who Gets MS, parasites are another possible risk factor in the development of MS. Research has found that parasites can modulate the immune system and dampen its responses. People who have parasites are less likely to be diagnosed with MS, and as conditions in different countries become cleaner with fewer parasites the number of individuals being diagnosed is increasing in these parts of the world. […] Another factor linked to MS is cigarette smoking. Women who smoke are 1.6 times more likely to develop MS than women who are non-smokers. Individuals with MS who smoke also appear to be at a much greater risk of experiencing a more rapid progression of their disease. […] Other potential causes continue to be investigated, some of which show promise, while others create much controversy within the MS community. Receiving a great amount of attention during recent years is the possible connection between chronic cerebrospinal venous insufficiency (CCSVI) and MS. CCSVI is a complex condition involving changes in blood flow from the brain back to the heart, which some researchers theorize could possibly lead to activation of the immune system, excess iron deposits, loss of myelin, and other nervous system damage.

• #1 Causes of MS | MS Trust

  https://mstrust.org.uk/information-support/about-ms/causes-ms

  It is known that multiple sclerosis is more common in countries further from the equator. One explanation for this observation may be that a lower exposure to sunlight results in a higher incidence of MS. […] There is increasing evidence that smoking is a significant risk factor in MS. Smoking may cause lung damage that ultimately makes the central nervous system vulnerable to attack by immune cells. […] An increased prevalence of MS has matched an increase in obesity in the Western World. Some scientists believe that there is a causal link between them. […] Some people with MS feel that they developed MS as a direct result of some stressful event or trauma. The evidence on this connection is mixed. […] In 2011, a study suggested that the combined effect of exposure to the Epstein Barr virus and low levels of vitamin D could increase the risk of developing multiple sclerosis.

• #1 Unravelling the causes of MS – MS Australia

  https://www.msaustralia.org.au/unravelling-the-causes-of-ms/

  Numerous studies have shown that smoking significantly increases your chances of developing MS. Smokers, and people exposed to second hand smoke, are almost two times more likely to develop MS and more likely to develop progressive forms of MS. […] Some studies have linked stress with the risk of developing MS, however, peoples different coping mechanisms and response to stressful events make this connection difficult to confirm. […] There is a great deal of interest in the role that nutrition and diet may play in the development and also the management of MS. […] Numerous studies have shown that being overweight/obese, particularly during adolescence, is associated with a 2-3 fold increase in the risk of developing MS. […] So, in conclusion, how does MS develop? Well it is a complex interaction between genetics and the environment.

• #1

  https://www.nationalgeographic.com/science/article/multiple-sclerosis-ms-cause-treatment-ebv

  MS affects the central nervous system, the brain and spinal cord. The immune system attacks sheaths of a material called myelin that surround nerve fibers. […] Theres no definitive cause of MS, but there is a prominent lead: the Epstein-Barr virus, known as EBV. In a study of over 10 million adults, the risk of developing MS increased by over 30 fold after EBV infection, researchers reported in Science back in 2022. […] Ascherio likens the connection between the virus and MS to the connection between smoking and cancer. Smoking causes lung cancer, but most smokers will never get lung cancer, he says. So, EBV could cause MS, but most people infected with EBV wont develop the disease. EBV may not be the one definitive cause of MS, but for now, its the leading culprit. […] Beyond EBV infections, other factors may increase the risk of MS. Women are about three times more likely to get MS, and scientists dont know why. One theory is that women are more susceptible to autoimmune issues because of how responsive their immune systems must be to tolerate the foreign DNA of a fetus, Bove says. […] Blood relatives of those with MS are also more likely to develop the disease. This doesnt mean MS is inherited, but genetic variants associated with it could be. Smoking, obesity and vitamin D deficiency are also associated with MS.

• #1 Possible causes and risk factors of MSEnvelope icon

  https://multiplesclerosisnewstoday.com/risk-factors-for-multiple-sclerosis/

  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. […] 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. […] People who have ever smoked cigarettes are at a roughly 50% higher risk of developing MS than those who never smoked. […] 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.

• #1 Early Signs of Multiple Sclerosis | Rush

  https://www.rush.edu/news/early-signs-multiple-sclerosis

  MS affects more than 2.3 million people globally. […] Though MS is not contagious or even directly inherited, some factors may increase the risk for this disease, including the following: […] „It tends to be a disease of women of reproductive age, so those from ages 18 to 50 receive the bulk of new diagnoses, with a median age of diagnosis being around 30 to 32,” Shoemaker says. […] The risk of developing MS is about 1 in 750 to 1,000 people in the general population. […] It increases, however, when a first-degree relative, such as parents, siblings and children, have the disease. […] Shoemaker also cites other specific factors, either alone or in combination that may contribute to the disease, which include the following: […] „From some of the longer duration studies, detecting MS earlier and starting MS therapies earlier tend to improve the chances of having a good long-term outcome.”

• #1 What Causes Multiple Sclerosis?

  https://www.everydayhealth.com/multiple-sclerosis/what-causes-ms/

  Studies have shown that obesity in childhood and adolescence, particularly in girls, increased the risk of developing MS at a later age. […] Your risk of developing MS increases slightly if you have other autoimmune disorders such as thyroid disease, pernicious anemia, psoriasis, type 1 diabetes, or inflammatory bowel disease. […] Research has suggested that previous infection with the Epstein-Barr virus (EBV, which causes mononucleosis) is linked to a higher risk of developing MS. […] Researchers in Sweden found that concussion (brain injury) between the ages of 11 and 20 is associated with a higher risk of MS and individuals who have had more than one concussion have an even higher risk of developing MS than those who have only had one. […] Prior studies have suggested that white people, particularly those of Northern European descent, are at highest risk of developing MS and that people of Asian, African, or Native American descent have the lowest risk. […] Most people are diagnosed with MS between age 20 and 50, but children and older adults can also develop the disease. […] A large study found that living near major roads was linked with higher incidence of multiple sclerosis and other neurological disorders.

• #1 Natural language processing analysis of the theories of people with multiple sclerosis about causes of their disease | Communications Medicine

  https://www.nature.com/articles/s43856-024-00546-3

  Of note, EBV had the fewest mentions among the four established risk factors. […] What also stands out from our analysis is that around 53.7% of participants reported stress-related factors including mental distress, stress, relationship/family problems, or adverse childhood experiences as potential risk factors for MS. […] This shows that mental health and related experiences are highly relevant to persons with MS and are perceived as influencing their lives in many ways. […] Our findings suggest that persons with MS associated their disease with a variety of factors. […] Participants varied in the degree to which they were convinced of their theories. […] Participants also noted and reported instances of the co-occurrence or sequential occurrence of risk factors. […] From their perspective, there may be an intuitive inclination to attribute the symptoms to the vaccine and antibiotics. […] Our study also revealed several discrepancies between current scientific evidence and theories that persons with MS have about risk factors for MS. […] This may have direct implications for public health efforts, including vaccination campaigns.

• #1 Multiple Sclerosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1146199-overview

  A controversial hypothesis proposes a vascular rather than an immunologic cause for some cases of MS. In 2008, Paolo Zamboni described an association between MS and chronic cerebrospinal venous insufficiency (CCSVI). […] The CCSVI hypothesis posits that stenosis of the main extracranial venous outflow pathways results in compromised drainage and a high rate of cerebral venous reflux. […] Worldwide anecdotal reports suggesting a connection between hepatitis B vaccination and MS prompted the US Centers for Disease Control and Prevention (CDC) to investigate this possibility. The CDC concluded that the weight of the available scientific evidence does not support the suggestion that hepatitis B vaccine causes or worsens MS.

• #1 Possible Causes of Multiple Sclerosis | MSAA

  https://mymsaa.org/ms-information/overview/possible-causes/

  While this theory has a large following, CCSVI also has a great amount of opposition. Despite the controversy, some patients have opted for risky treatments on their own, sometimes going to clinics outside of the country. A recent, large study in Italy did not support the link of CCSVI and MS. Numerous other CCSVI research projects are still in progress, including research in Europe and the United States.

• #1 What Actually Causes Multiple Sclerosis? An MS-Specialist’s Take.

  https://www.drgretchenhawley.com/blog/what-actually-causes-multiple-sclerosis

  Multiple sclerosis (MS) is a complex and often misunderstood condition that affects the central nervous system, including the brain, spinal cord, and optic nerves. […] While researchers are still working to fully understand MS, we do know that its caused by a mix of factors that involve the immune system, genetics, and the environment. […] The exact cause of MS is still unknown, but researchers believe its triggered by a combination of genetic predisposition, environmental factors, and an abnormal immune response. In other words, theres no single causeits more like a mix of risk factors coming together. […] At its core, MS is an autoimmune disease. This means your immune systemdesigned to protect you from harmful invaders like virusesmistakenly attacks your own body instead. In MS, the immune system targets myelin as if it were an enemy.

• #1 The Probable Infectious Origin of Multiple Sclerosis

  https://www.mdpi.com/2673-4087/4/3/19

  It is generally accepted that the etiology of MS is multifactorial and believed to be a complex interplay between genetic susceptibility, environmental factors such as smoking and obesity, and infectious agents that lead to immune dysregulation and CNS inflammation. […] While the exact cause of MS is not yet fully understood, it is believed that risk of developing the disease is strongly influenced by an individual’s genetic makeup. […] More recently, genome-wide association studies (GWAS) identified more than 200 genetic variants associated with increased MS risk, with approximately 30 associated with the major histocompatibility complex (MHC) locus. […] In addition to identifying variants in immune function that contribute to MS risk, genetic studies have also provided insight into the biology of the disease. These genetic factors are not sufficient on their own to cause MS, and environmental factors such as viral infections, smoking, and vitamin D deficiency also play important roles in disease development.

• #1 What causes multiple sclerosis, is it hereditary? | Paris Brain Institute

  https://parisbraininstitute.org/disease-files/multiple-sclerosis-ms/what-causes-multiple-sclerosis-it-hereditary

  Although multiple sclerosis was described by Charcot more than a century and a half ago, the causes of this disease of the central nervous system are still unknown. […] Multiple sclerosis (MS) is not an inherited disease. It is a multifactorial condition. Some environmental factors have now been identified without a clear causal relationship. Similarly, genetic predisposition may also be present. The latter can be defined as a combination of genetic variants, which confers a greater risk of developing the disease. It is considered that this alone is not sufficient for the disease to appear, but that it is a breeding ground for its development. It should be noted that most of the genetic variants identified are associated with so-called immune genes, that is, genes involved in inflammation.

• #1 What Causes Multiple Sclerosis?

  https://www.verywellhealth.com/what-causes-multiple-sclerosis-7965715

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

• #1 The Etiology of Multiple Sclerosis

  https://www.neurologylive.com/view/the-etiology-of-multiple-sclerosis

  The underlying biology of MS [multiple sclerosis] is both fascinating and complex. Its a real interaction between genetic factors and environmental factors. This is an immune-mediated condition where, probably, the events that lead to the development of MS biologically occur within the first decade of life. […] Factors that seem to promote this include certain genetic predisposition, exposure to certain viruses early on, such as EBV [Epstein-Barr virus], low vitamin D levels, or exposure to certain pollutants, toxic factors, or smoke. […] What seems to be clear is that Epstein-Barr viral exposure early on is a factor, as is the fact that people who get infectious mononucleosis, which is caused by Epstein-Barr virus, have an increased risk of developing MS. […] What likely happens is, in the process of fighting off that viral exposure or that viral infection, a misdirect occurs. Immune cells, probably T cells aided by B cells, become refocused on what they think is Epstein-Barr virus, but is really the persons own bits of myelin basic protein or other fragments of myelin that are floating around in the bloodstream. The immune cells see these little protein fragments of self and act as if they were a foreign entity and mount an immune attack that then leads to the symptoms of the condition.

• #2

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5241505/

  Multiple sclerosis (MS) is a chronic inflammatory disease characterized by central nervous system (CNS) lesions that can lead to severe physical or cognitive disability as well as neurological defects. […] Although the etiology and pathogenesis of MS remains unclear, the present documents illustrate that the cause of MS is multifactorial and include genetic predisposition together with environmental factors such as exposure to infectious agents, vitamin deficiencies, and smoking. […] The etiology of MS remains unclear, however it can be considered a multifactorial disease and include a genetic predisposition combined with environmental influences. […] The precise cause of MS is unknown. Nonetheless, genetic predispositions combined with environmental influences play an important role in the pathogenesis of this disease.

• #2 Multiple sclerosis – Wikipedia

  https://en.wikipedia.org/wiki/Multiple_sclerosis

  Multiple sclerosis is an autoimmune disease with a combination of genetic and environmental causes underlying it. Both T-cells and B-cells are involved, although T-cells are often considered to be the driving force of the disease. The causes of the disease are not fully understood. The Epstein-Barr Virus (EBV) has been shown to be directly present in the brain of most cases of MS and the virus is transcriptionally active in infected cells. EBV nuclear antigens are believed to be involved in the pathogenesis of multiple sclerosis, but not all people with MS have signs of EBV infection. Dozens of human peptides have been identified in different cases of the disease, and while some have plausible links to infectious organisms or known environmental factors, others do not. […] Failure of both central and peripheral nervous system clearance of autoreactive immune cells is implicated in MS development. The thymus is responsible for the immune system’s central tolerance, where autoreactive T-cells are killed without being released into circulation. A similar mechanism kills autoreactive B-cells in the bone marrow. Some autoreactive T-cells B-cells may escape these defense mechanisms, which is where peripheral immune tolerance defenses take action by preventing them from causing disease. However, these additional lines of defense can still fail.

• #2 Multiple Sclerosis

  https://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/neurology/multiple_sclerosis/

  Multiple Sclerosis (MS) is a chronic inflammatory, demyelinating, and neurodegenerative disorder of the central nervous system (CNS) that affects the white and grey matter of the brain, spinal cord, and optic nerve. […] The exact cause of inflammation remains unclear, but an autoimmune response directed against CNS antigens is suspected. […] In progressive MS, inflammation is a less defining pathological hallmark. Instead, progressive MS is characterized by neurodegeneration of the white and grey matter resulting in brain and spinal cord atrophy on a background of mild-moderate inflammation. […] An important implication of this hypothesis is that the accumulation of irreversible tissue damage limits the potential for anti-inflammatory disease modifying therapies (DMTs) when used in the progressive stage of the disease.

• #2 Multiple Sclerosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK499849/

  Although the exact etiology of multiple sclerosis is unknown, factors involved in pathogenesis are broadly grouped into 3 categories immune factors, environmental factors, and genetic associations. […] Dysimmunity with an autoimmune attack on the CNS is the leading hypothesized etiology of multiple sclerosis. The postulated „outside-in” mechanism involves CD4+ proinflammatory T cells among various proposed mechanisms. […] Environmental factors, such as latitudinal gradients observed in various countries, have been extensively studied. […] Vitamin D deficiency has been considered a possible etiology for the noted predisposition of populations in higher latitudes to multiple sclerosis. […] Patients with biological relatives with multiple sclerosis have a heightened risk of developing the condition. […] The human leukocyte antigen (HLA) DRB1*1501 allele strongly correlates with multiple sclerosis and is one of the most studied alleles relative to multiple sclerosis linkage. […] Polymorphisms in several genes may be associated with a slightly increased risk of multiple sclerosis.

• #2

  https://www.healio.com/clinical-guidance/multiple-sclerosis/etiology-and-risk-factors-overview

  The exact etiology of multiple sclerosis (MS) is not known, but its development is now known to be influenced by an interplay of background genetic variants and environmental triggers, including both lifestyle factors and exogenous factors most prominently, Epstein-Barr virus (EBV) infection. […] That genetic factors play a role in the development of MS is evidenced by the clinical concordance rate (i.e., the proportion of pairs of individuals that share a disorder) of 25-30% in monozygotic twins, compared to 3-7% of dizygotic twins. This is further underscored by an increased lifetime risk of MS in first degree relatives (~3%) and second-degree relatives (~1%), which is much greater than in the general population (0.1-0.3%). […] A number of lifestyle and environmental factors have been linked to increased risk of MS, including EBV infection, smoking (active or passive), adolescent obesity and low sun exposure. Seropositivity to EBV appears to be the strongest and best supported risk factor.

• #2 Multiple sclerosis – Wikipedia

  https://en.wikipedia.org/wiki/Multiple_sclerosis

  MS is not considered a hereditary disease, but several genetic variations have been shown to increase its risk. Some of these genes appear to have higher expression levels in microglial cells than expected by chance. The probability of developing MS is higher in relatives of an affected person, with a greater risk among those more closely related. An identical twin of an affected individual has a 30% chance of developing MS, 5% for a nonidentical twin, 2.5% for a sibling, and an even lower chance for a half-sibling. If both parents are affected, the risk in their children is 10 times that of the general population. MS is also more common in some ethnic groups than others. […] The prevalence of MS from a geographic standpoint resembles a gradient, with it being more common in people who live farther from the equator (e.g., those who live in northern regions of the world), although exceptions exist. The cause of this geographical pattern is not clear, although exposure to ultraviolet B (UVB) radiation and vitamin D levels may be a possible explanation. For example, those who live in northern regions of the world have less exposure to UVB radiation and lower levels of vitamin D, and a higher risk for developing MS. Inversely, those who live in areas of higher sun exposure and increased UVB radiation have a decreased risk of developing MS.

• #2 Multiple Sclerosis: Symptoms & Causes | NewYork-Presbyterian

  https://www.nyp.org/neuro/multiple-sclerosis

  The exact causes of multiple sclerosis are unclear, though it is considered an autoimmune disease in which the immune system attacks the central nervous system. […] Medical professionals and researchers are studying possible causes that may trigger this immune system response. Potential triggers include infections, viruses, and environmental and genetic factors.

• #2 Multiple sclerosis – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/multiple-sclerosis/symptoms-causes/syc-20350269

  If one of your parents or siblings has had MS, you are at higher risk of developing the disease. […] A variety of viruses have been linked to MS, including Epstein-Barr. Epstein-Barr is the virus that causes infectious mononucleosis. […] People with white skin, particularly those of Northern European descent, have the highest risk of developing MS. […] MS is far more common in places with temperate climates. These include Canada, the northern United States, New Zealand, southeastern Australia and Europe. […] Having low levels of vitamin D and low exposure to sunlight is linked to a greater risk of MS. […] People who are obese or were obese in childhood have an increased risk of multiple sclerosis. […] You have a slightly higher risk of developing MS if you have other autoimmune conditions. These may include thyroid disease, pernicious anemia, psoriasis, type 1 diabetes or inflammatory bowel disease. […] People who smoke have a higher risk of relapsing-remitting MS than people who don’t smoke.

• #2 Multiple Sclerosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1146199-overview

  Another hypothesis is that a virus may infect the immune system, activating self-reactive T cells (myelin reactive) that would otherwise remain quiescent. A virus that infects cells of the immune and nervous systems can possibly be reactivated periodically and thus lead to acute exacerbations in MS. […] Geography is clearly an important factor in the etiology of MS. The incidence of the disease is lower in the equatorial regions of the world than in the southernmost and northernmost regions. […] Low levels of vitamin D have been proposed as one environmental factor contributing to the development of MS. Vitamin D has a role in regulating immune response, by decreasing production of proinflammatory cytokines and increasing production of anti-inflammatory cytokines; also, high circulating levels of vitamin D appear to be associated with a reduced risk of MS.

• #2 Causes of MS | MS Trust

  https://mstrust.org.uk/information-support/about-ms/causes-ms

  It is known that multiple sclerosis is more common in countries further from the equator. One explanation for this observation may be that a lower exposure to sunlight results in a higher incidence of MS. […] There is increasing evidence that smoking is a significant risk factor in MS. Smoking may cause lung damage that ultimately makes the central nervous system vulnerable to attack by immune cells. […] An increased prevalence of MS has matched an increase in obesity in the Western World. Some scientists believe that there is a causal link between them. […] Some people with MS feel that they developed MS as a direct result of some stressful event or trauma. The evidence on this connection is mixed. […] In 2011, a study suggested that the combined effect of exposure to the Epstein Barr virus and low levels of vitamin D could increase the risk of developing multiple sclerosis.

• #2 Possible causes and risk factors of MSEnvelope icon

  https://multiplesclerosisnewstoday.com/risk-factors-for-multiple-sclerosis/

  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. […] 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. […] 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.

• #2 What Causes Multiple Sclerosis?

  https://www.verywellhealth.com/what-causes-multiple-sclerosis-7965715

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

• #2 Lectures:   Etiology

  https://library.med.utah.edu/kw/ms/etiology.html

  Infectious agents have been proposed as inciters of the MS. Some viral isolates have been found in the CNS of the patients with MS. However, this data is not consistent and thus far there has not been a viral protein or a group of viruses reliably identified in the CSF of patients with MS. […] There is a considerable interest in a theory that exposure to a virus may lead to immunopathologic condition resulting in MS. One possible explanation for this is molecular mimicry between viral and CNS proteins so that antiviral response is mediated against myelin. „Molecular mimicry” means shared molecular homology between viral proteins and some normal human proteins. In MS, homology between viral peptides and myelin antigens is established. Viral persistency, latency and periodic inactivation could be of possible significance. A recent investigation suggests that HHV6 (Roseola virus) is associated with areas of demyelination in MS patients. Viral infections also are known to provoke relapses of the disease.

• #2 What Causes Multiple Sclerosis?

  https://www.everydayhealth.com/multiple-sclerosis/what-causes-ms/

  MS isnt an inherited disease, which means families dont pass it from one generation to the next. However, you can inherit genes that put you at greater risk of developing MS. […] Women are 2 to 3 times more likely than men to be diagnosed with relapsing-remitting MS, the most common type of MS. […] There are a number of other factors that are associated with an increased risk for developing multiple sclerosis, although whether any of them are causative is unknown. […] Smokers and people who are exposed to secondhand smoke have an increased risk of developing MS. […] A growing body of evidence suggests that vitamin D deficiency may increase a persons risk of developing multiple sclerosis. […] People who live in more temperate climates like Europe, southern Canada, and the United States have a slightly higher risk of MS than those who live closer to the equator, Greenfield says.

• #2 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Multiple-Sclerosis-Causes.aspx

  Multiple sclerosis is an autoimmune disease. Usually, the immune system protects the body against invading microbes or foreign bodies. Autoimmune diseases, on the other hand, occur when the immune system mistakes healthy body tissue for foreign or damaged tissue. […] The exact cause of multiple sclerosis is not clearly understood, but genetic and environmental factors seem to play a role in causing the condition. […] There is evidence that vitamin D deficiency plays a significant role in the development of MS, which could explain its geographical patterns. […] Studies have also shown certain lifestyle choices to be associated with a higher risk of MS. Smoking is linked to an increased risk of developing MS and increased severity and rapid progression of the disease. […] Since no single gene has yet been identified as causing multiple sclerosis, it is not classified as a genetic disease. However, researchers have shown that individuals with a relative who has had MS are more likely to develop it.

• #2 Possible causes and risk factors of MSEnvelope icon

  https://multiplesclerosisnewstoday.com/risk-factors-for-multiple-sclerosis/

  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. […] 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. […] People who have ever smoked cigarettes are at a roughly 50% higher risk of developing MS than those who never smoked. […] 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.

• #2 What Causes Multiple Sclerosis?

  https://www.everydayhealth.com/multiple-sclerosis/what-causes-ms/

  Studies have shown that obesity in childhood and adolescence, particularly in girls, increased the risk of developing MS at a later age. […] Your risk of developing MS increases slightly if you have other autoimmune disorders such as thyroid disease, pernicious anemia, psoriasis, type 1 diabetes, or inflammatory bowel disease. […] Research has suggested that previous infection with the Epstein-Barr virus (EBV, which causes mononucleosis) is linked to a higher risk of developing MS. […] Researchers in Sweden found that concussion (brain injury) between the ages of 11 and 20 is associated with a higher risk of MS and individuals who have had more than one concussion have an even higher risk of developing MS than those who have only had one. […] Prior studies have suggested that white people, particularly those of Northern European descent, are at highest risk of developing MS and that people of Asian, African, or Native American descent have the lowest risk. […] Most people are diagnosed with MS between age 20 and 50, but children and older adults can also develop the disease. […] A large study found that living near major roads was linked with higher incidence of multiple sclerosis and other neurological disorders.

• #2 Multiple Sclerosis | MS | MedlinePlus

  https://medlineplus.gov/multiplesclerosis.html

  Multiple sclerosis (MS) is a nervous system disease that affects your brain and spinal cord. […] No one knows what causes MS. It may be an autoimmune disease, which happens when your immune system attacks healthy cells in your body by mistake. […] Multiple sclerosis affects women more than men.

• #2

  https://journals.lww.com/md-journal/fulltext/2024/02230/review_of_multiple_sclerosis__epidemiology,.15.aspx

  Multiple sclerosis (MS) emergence is a perplexing matter; its origins remain a mystery. However, newer investigations infer that it arises from a fusion of genetic vulnerability and environmental agents from development to young adulthood. Specific factors deemed highly culpable in regard to genetic disposition for MS and ability to make an impact include a lack of vitamin D, birth season, tobacco use, and exposure to Epstein-Barr virus.[7,8] […] In MS, cytokine-producing T cells with a preference for myelin are frequently immunogenic, resulting in Th1-like proinflammatory responses. Myelin destruction in MS appears to be primarily initiated by T-helper cells (cluster of differentiation 4 [CD4]+). In particular, autoreactive CD4+cells, particularly the Th1 variant, appear to be the main culprits and are likely activated after viral infection in the periphery.

• #2 Possible Causes of Multiple Sclerosis | MSAA

  https://mymsaa.org/ms-information/overview/possible-causes/

  Also noted in the section, Who Gets MS, parasites are another possible risk factor in the development of MS. Research has found that parasites can modulate the immune system and dampen its responses. People who have parasites are less likely to be diagnosed with MS, and as conditions in different countries become cleaner with fewer parasites the number of individuals being diagnosed is increasing in these parts of the world. […] Another factor linked to MS is cigarette smoking. Women who smoke are 1.6 times more likely to develop MS than women who are non-smokers. Individuals with MS who smoke also appear to be at a much greater risk of experiencing a more rapid progression of their disease. […] Other potential causes continue to be investigated, some of which show promise, while others create much controversy within the MS community. Receiving a great amount of attention during recent years is the possible connection between chronic cerebrospinal venous insufficiency (CCSVI) and MS. CCSVI is a complex condition involving changes in blood flow from the brain back to the heart, which some researchers theorize could possibly lead to activation of the immune system, excess iron deposits, loss of myelin, and other nervous system damage.

• #2 What Causes Multiple Sclerosis? Criteria for New Hypotheses

  https://austinpublishinggroup.com/clinical-neurology/fulltext/ajcn-v1-id1002.php

  The most wellknown hypothesis suggests that MS is an autoimmune process which leads to neuroinflammation and demyelination. […] The second hypothesis suggests that MS is an infectious disease. […] The third hypothesis suggests that patients with MS have chronic cerebrospinal venous insufficiency (CCSVI) causing delayed venous outflow from the brain and spinal cord. […] However, they do not explain the key epidemiological finding of decreased MS prevalence in Asian countries. […] Therefore, two mandatory criteria are proposed for a new biological factormechanism hypothesized to be a MS cause: The new hypothesis has to explain why the disease is restricted to the CNS and causes both inflammation and neurodegeneration. […] The new hypothesis has to explain why the disease has low prevalence in Asia.

• #2 Natural language processing analysis of the theories of people with multiple sclerosis about causes of their disease | Communications Medicine

  https://www.nature.com/articles/s43856-024-00546-3

  Of note, EBV had the fewest mentions among the four established risk factors. […] What also stands out from our analysis is that around 53.7% of participants reported stress-related factors including mental distress, stress, relationship/family problems, or adverse childhood experiences as potential risk factors for MS. […] This shows that mental health and related experiences are highly relevant to persons with MS and are perceived as influencing their lives in many ways. […] Our findings suggest that persons with MS associated their disease with a variety of factors. […] Participants varied in the degree to which they were convinced of their theories. […] Participants also noted and reported instances of the co-occurrence or sequential occurrence of risk factors. […] From their perspective, there may be an intuitive inclination to attribute the symptoms to the vaccine and antibiotics. […] Our study also revealed several discrepancies between current scientific evidence and theories that persons with MS have about risk factors for MS. […] This may have direct implications for public health efforts, including vaccination campaigns.

• #2 Multiple Sclerosis (MS) > Fact Sheets > Yale Medicine

  https://www.yalemedicine.org/conditions/multiple-sclerosis-ms

  Multiple sclerosis (MS) is estimated to affect almost 1 million Americans and the disease actually comes in many different forms. […] For years, its root causes were completely unknown. But researchers including neurologist David Hafler, MD, who directs the Yale Medicine Neurology Department have begun to identify the genetic and environmental factors that contribute to the development and progression of MS. […] While the cause of MS is still unknown, the latest research indicates that the disease may develop when specific genetic mutations are set off by environmental factors. […] Research has determined that if a patient’s mother or father had MS, she has a higher risk of developing it. […] In the Hafler Lab at Yale Medicine, Dr. Hafler and his team of researchers have made a major breakthrough in identifying the genetic roots of multiple sclerosis, including more than 150 genetic variants common in people with MS.

• #2 Multiple Sclerosis (MS): Risk Factors, Genetics, and Expert Research

  https://www.healthline.com/health/multiple-sclerosis/possible-causes

  Other risk factors may also increase your chances of developing MS. These include: Sex: Females are at least 2 to 3 times more likely to develop relapsing-remitting multiple sclerosis (RRMS) than males, according to the NMSS. […] While the exact cause of MS is a mystery, researchers have identified four important risk factors for MS. […] Its believed that these four factors interact with each other in a complex manner to raise a persons risk of developing MS.

• #2 Multiple sclerosis (MS) – symptoms, treatment and types | healthdirect

  https://www.healthdirect.gov.au/multiple-sclerosis-ms

  Multiple sclerosis (MS) is a chronic illness that affects your central nervous system. Your nerve cells are surrounded by a layer called myelin. Myelin protects your nerves and helps them send signals quickly from your brain to the rest of your body. […] In MS, your immune system attacks the myelin layer and damages it. This causes your nerves to become exposed and scarred. As a result, your nerves cant send signals around your body properly. […] The cause of MS is not known, but there are several factors that make you more likely to develop MS. These include: having a close relative with MS or another autoimmune illness, low vitamin D levels, living further away from the equator possibly because this usually means you have a lower level of vitamin D, previously having Epstein-Barr virus (glandular fever), smoking, living with obesity.

• #2 What Causes Multiple Sclerosis (MS)? | National MS SocietyNational Multiple Sclerosis Society LogoNational Multiple Sclerosis Society LogoOpen search

  https://www.nationalmssociety.org/understanding-ms/what-is-ms/what-causes-ms

  MS diagnoses occur more frequently in areas farther from the equator. […] Growing evidence suggests that vitamin D plays an important role in MS. […] More and more evidence also indicates that smoking plays an important role in MS. […] Several studies show that obesity in childhood and adolescence increases the risk of MS. […] Scientists are investigating the role of many viruses and bacteria in the development of MS. […] This does not mean that MS is an infectious disease. However, inactive viruses may play a role in triggering MS symptoms and activity. […] MS is not an inherited disease. It is not passed down from generation to generation. But people can inherit genetic risk. […] Researchers have investigated many possible causes of MS without turning up evidence of a link.

• #2

  https://www.healio.com/clinical-guidance/multiple-sclerosis/etiology-and-risk-factors-overview

  As shown in Table 1-1, EBV infection, adolescent obesity and smoking interact with genetic predisposition factors (specifically, polymorphisms in HLA loci) to substantially increase the risk of MS. This suggests a mechanistic convergence of these factors, most likely at the level of adaptive immunity, which promotes an autoimmune response against the central nervous system (CNS).

• #2 Early Signs of Multiple Sclerosis | Rush

  https://www.rush.edu/news/early-signs-multiple-sclerosis

  MS affects more than 2.3 million people globally. […] Though MS is not contagious or even directly inherited, some factors may increase the risk for this disease, including the following: […] „It tends to be a disease of women of reproductive age, so those from ages 18 to 50 receive the bulk of new diagnoses, with a median age of diagnosis being around 30 to 32,” Shoemaker says. […] The risk of developing MS is about 1 in 750 to 1,000 people in the general population. […] It increases, however, when a first-degree relative, such as parents, siblings and children, have the disease. […] Shoemaker also cites other specific factors, either alone or in combination that may contribute to the disease, which include the following: […] „From some of the longer duration studies, detecting MS earlier and starting MS therapies earlier tend to improve the chances of having a good long-term outcome.”

• #3 Primary Progressive Multiple Sclerosis (PPMS): Symptoms

  https://my.clevelandclinic.org/health/diseases/14202-primary-progressive-multiple-sclerosis-ppms

  The exact cause of MS is unknown. Research suggests it could be related to changes in your DNA (genetic predisposition) that make you more likely to have an autoimmune condition. Genetics only play a small part in MS, so your risk of passing the condition onto your future children is low. […] Environmental factors can also play a role in developing MS. An example is exposure to bacteria or viruses. […] If you have MS, your immune system mistakenly attacks healthy parts of your central nervous system, which causes symptoms.

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