Many causes of Multiple Sclerosis

Multiple sclerosis research is currently enjoying particular success. Thanks to a range of different therapeutic approaches, patients are often virtually symptom-free despite many years of suffering from the neurological disorder. There still are young women in their early forties who are confined to a wheelchair and need domestic help. But such cases are becoming rarer. And there are increasing numbers of cases such as that of a woman over 60 who only finds it difficult to walk long distances but lives independently. 

The courses of the disease vary so widely because multiple sclerosis is not a disease with a uniform presentation but encompasses different forms of progression. More than 80 percent of patients initially suffer from relapsing-remitting MS (RRMS), in which the symptoms partially or even completely regress between outbreaks. However, the disease can also progress constantly from the outset or be interrupted by periods of remission (primary progressive MS). In about half of all patients with RRMS, the disease progresses to a progressive form within ten years; this is referred to as secondary progressive MS (SPMS).

Both a genetic predisposition and various triggers such as the environment and lifestyle fuel MS. “There is no single pathological element,” says Klarissa H. Stürner, senior physician at the Neuroimmunology Outpatient Clinic at Kiel University Hospital. However, genes are one of the main suspects. It has long been known that this disease of the central nervous system has a hereditary component. Twin studies have shown that the risk of the second twin also developing MS is 20-30 percent. However, the hereditary risk is not concentrated in a single gene. The heritability of multiple sclerosis is based on variants in many genes, with each of these variants contributing only a small part to the overall risk of disease.

An international consortium compared the genetic material of nearly 50,000 MS patients with almost 70,000 healthy control subjects. They found more than 230 gene variants that influence the risk of developing MS. Most of these affect peripheral immune cells and microglia in the brain. The picture is further complicated by the fact that the risk of developing the disease depends on other gene variants than the risk of disease progression.
 

Infection with the same virus that causes Pfeiffer's glandular fever – which many people contract in childhood and adolescence – may play a decisive role in the development of the MS: Epstein-Barr viruses (EBV) attack B lymphocytes and multiply in them. Newly infected individuals sometimes develop a fever and aching limbs, lose their appetite, and experience extreme fatigue for weeks. The infection usually progresses silently, especially in children. In approximately 95 percent of the population, the virus can be detected in the B lymphocytes in adulthood, where it lies dormant. “The Epstein-Barr virus is not the cause of multiple sclerosis. But it activates the immune system, especially the B lymphocytes, in such a way that the disease can occur later,” says Volker Siffrin, group leader at the Neuroimmunology Laboratory of the Max Delbrück Center for Molecular Medicine in Berlin.

Based on many years of experience with MS patients, Stürner adds that she has never seen an MS patient who has not had contact with Epstein-Barr viruses. If all B lymphocytes, the home of the viruses, are eliminated with medication, the progression of the disease slows down significantly. The causal role of EBV has not yet been proven, but recent research findings indicate that infection with EBV could be a prerequisite for the development of MS. 

The maturation of the immune system is also influenced by another factor that repeatedly crops up in studies on multiple sclerosis: sunlight. The more frequently and regularly the skin is exposed to the sun, the more vitamin D is produced in the upper layer of skin. "This substance has many functions, almost like a hormone, and regulates how aggressive the immune system is. Too low vitamin D levels make the immune system “hyperactive,” so that autoimmune diseases such as multiple sclerosis have an easier time later on," explains Stürner. Perhaps this is one reason why multiple sclerosis is so rare in the sunny equatorial regions and becomes more common towards the poles.

However, this means that it is not only genes that pave the way for this neurological disorder, over which we have no control. Rather, we can also influence some factors ourselves, such as smoking and possibly obesity. “And living indoors – away from the sun – is a recent phenomenon in evolutionary terms, to which the immune system has not yet been able to adapt,” adds Siffrin. 

Overall, doctors blame the Western lifestyle for the continuing increase in the incidence of multiple sclerosis in industrialized nations. In countries such as the US, Canada, the UK, Scandinavia, and Germany, it has increased fivefold in some cases since the 1970s. Although earlier diagnosis and higher life expectancy of patients also play a role, these factors alone are not sufficient to explain the trend. 

Women are particularly affected by this chronic nervous disorder. This is probably due to sex hormones and their effect on the immune system. Another reason is likely to be that they are smoking more and more frequently. According to a number of studies, smoking also increases the risk of developing multiple sclerosis by 50 percent. Swedish researchers have even been able to show that genetic risk factors and smoking increase the risk of disease. So, anyone who has a genetic predisposition to the disease and smokes increases their risk much more dramatically than the individual factors would suggest.

MS researchers are also interested in a peculiarity of the Western diet: food, especially ready meals and fast food, is comparatively salty in industrialized countries. However, such a diet could promote MS, as some researchers conclude from experiments with cell cultures and mice. Professor Ralf Linker, director of the Clinic and Polyclinic for Neurology at the University of Regensburg, considers this to be plausible, even if it has not yet been proven to be causal: “In regions with McDonald's, there are significantly more autoimmune diseases.”

Diet may also indirectly influence the risk of MS through the colonization of bacteria in the gut. Hartmut Wekerle, Professor Emeritus at the Max Planck Institute for Biological Intelligence in Martinsried, demonstrated this with stool samples and microorganisms taken directly from the small intestine of identical twins, only one of whom had MS. Symptoms were mainly observed in mice that had been colonized with samples from MS patients. For Wekerle, this is a strong indication that disease-causing microorganisms are present in the small intestine of people with MS. 

When asked about the causes of MS, researchers have found some possible answers and raised many new questions: Why, for example, do relapses decrease significantly during pregnancy, by as much as 80 percent in the last trimester? And why does the relapse rate increase slightly but measurably again after birth? “We don't know the causes,” says neurologist Professor Kerstin Hellwig from Bochum University Hospital. She and others suspect that hormones moderate the immune system and thus prevent the disease from progressing. “During pregnancy, the immune system has to adapt so that it does not reject another human being in its own body, the child, as foreign.” This observation also underscores the fact that MS is a multifactorial event that will certainly keep scientists busy for a long time to come.

First published on April 28, 2017
Last updated on October 7, 2025