risk factors

The idea that a vitamin D deficiency contributes to the risk of developing multiple sclerosis (MS) has been challenged in a recent study that examined subtle differences in a protein involved in vitamin D metabolism in people from different ethnic backgrounds. The study, “Vitamin D-Binding Protein…

Pregnant women with multiple sclerosis (MS) exposed to Tysabri (natalizumab) in the first trimester had higher rates of miscarriage and major birth defects in their babies, than women left untreated or treated with interferon beta, a study shows. Although higher, these rates were similar to those in the general…

One of the many disease-modifying therapies (DMTs) that I’ve been on over the many years of my treatment for MS is Tysabri (natalizumab). It worked well, holding the progression of my MS at bay for the several years that I received the infusions. I’d probably still be on it…

A molecule triggered by the male hormone testosterone protects male mice from developing multiple sclerosis, Northwestern Medicine researchers report. Their discovery may help explain why MS affects more women than men. It could also lead to targeted therapies to protect women against the disease. The study, “…

Researchers have found a link between variations in two genes that control our 24-hour biological clock and the risk of a person developing multiple sclerosis. The study, “Association of circadian rhythm genes ARNTL/BMAL1 and CLOCK with multiple sclerosis,” was published in the journal PLOS ONE. Scientists know MS…

Multiple sclerosis patients with high relapse rates but less physical impairment before starting on  Novartis’ Gilenya (fingolimod) are likely to experience a surge in disease activity if they stop the treatment, researchers in Turkey report. The study, which dealt with patients with relapsing forms of MS, referred to the surge as "severe disease reactivation," or SDR. Researchers published their article, “Factors Predictive of Severe Multiple Sclerosis Disease Reactivation After Fingolimod Cessation,” in the journal The Neurologist. Studies have shown that Gilenya, which the U.S. Food and Drug Administration approved in 2010, can benefit adults with relapsing MS. It reduces annualized relapse rates and prevents more brain lesions from forming, compared with standard interferon treatments. Lesions are damaged nerve cell areas. Despite its benefits, Gilenya is not recommended for patients with heart or liver problems, low levels of white blood cells, severe herpes virus infections or other infections. Also, patients who do not respond to Gilenya and women who are planning to become pregnant are advised to stop the treatment. Discontinuing Gilenya can lead to a return to pretreatment disease activity, or severe disease reactivation, in some patients. It is unclear why this happens and why it affects only some patients. To better understand what risk factors could be associated with reactivation, a team at Istanbul University compared the demographic and disease features of patients who developed SDR after stopping treatment with Gilenya. SDR was defined as including these elements within 6 months of Gilenya discontinuation: more than 5 gadolinium-enhanced lesions or a tumefactive demyelinating lesion detectable by magnetic resonance imaging, the disease progressing to the point that additional treatment with methylprednisolone or plasma exchange was required, and progressive physical disability reflected by a 1-point or more increase in patients' scores on the Expanded Disability Status Scale, or EDSS, Thirty-one patients at the university’s MS clinic who had discontinued Gilenya were included in the study. Eight experienced SDR and 11 relapses. The mean time for SDR patients' reactivation to occur was 2.6 months, researchers said. Patients had significantly higher levels of lymphocytes — white blood cells involved in autoimmunity — than during Gilenya treatment. When the team compared the disease features of SDR and non-SDR patients, they found that SDR patients had significantly higher annualized relapse rates before starting Gilenya and lower EDSS scores. “A higher ARR [annualized relapse rate] is the major contributory factor toward development of SDR,” the researchers wrote. “Patients who had higher ARRs before fingolimod [Gilenya] treatment must be closely followed up both clinically and radiologically in terms of the early signs of severe reactivation,” they wrote. About 38 percent of the SDR patients failed to respond to steroid treatment. They received a plasma exchange, which led to moderate improvement in their condition. Based on this finding, the researchers suggested that “plasmapheresis [plasma exchange] must be considered in patients exhibiting steroid-refractory SDR.” "In conclusion, SDR may be observed within the first 3 months after cessation of fingolimod," the team wrote. "This may be explained by the rapid influx of lymphocytes into the CNS [central nervous system]. Patients with higher annualized relapse rates and lower Expanded Disability Status Scale scores before commencing fingolimod treatment were more likely to exhibit SDR."  

Iranian researchers have identified another herpes virus that may increase the risk of a person developing multiple sclerosis. The team identified the human herpesvirus 6, or HHV6, as a potential risk factor for MS through a meta-analysis of several studies. They published their findings, “Relationship of Human…

The U.S. Food and Drug Administration (FDA) has updated a safety bulletin about gadolinium-based contrast agents (GBCAs), after studies raised new concerns about them. Doctors often use GBCAs to diagnose multiple sclerosis (MS), monitor disease activity and verify the effectiveness of MS therapies. Gadolinium is a metal ion, or electrically charged molecule, that…

Multiple sclerosis patients with additional diseases, high cholesterol levels or a history of migraine headaches are more likely to experience relapses than other patients, a Canadian study shows. The report, “Comorbidity increases the risk of relapse in multiple sclerosis,” was published in the journal Neurology. Researchers…

There is often alarm and confusion about the JC virus, how we get it, and what it means to people with multiple sclerosis. This is my quick primer to help address these questions in a very basic way. What is the JC virus? The first person identified with this…

Magnetic resonance imaging (MRI) brain scans of children could reveal changes associated with multiple sclerosis (MS) before any symptoms are developed, according to a study by scientists at Yale University School of Medicine. The findings suggest that brain and spinal cord scans can identify children at high risk for developing MS.

A higher intake of dietary sodium, most often in the form of salt, does not increase the risk of developing multiple sclerosis (MS), Norwegian researchers concluded after analyzing data from more than 175,000 women. Their findings counter earlier evidence from experimental studies in cells and MS mouse models that suggested…

Diet can play an important role in whether children with relapsing multiple sclerosis have a relapse, researchers at the University of California, San Francisco argue. Their study demonstrated that a diet with a lot of fat increases the risk of a youngster having a relapse by 56 percent, with saturated fat tripling the risk. Eating a lot of vegetables, on the other hand, cuts the risk in half, the team said. Since children with MS tend to have relapses more often than adults, the researchers figured they would be a suitable group to study diet's impact on relapse. They recruited 219 children with relapsing-remitting MS or clinically isolated syndrome from 11 centers across the U.S. Clinically isolated syndrome is a condition that can evolve in MS. The research team use a questionnaire known as the Block Kids Food Screener to analyze what the youngsters ate. They tracked the children an average of almost two years, which was plenty of time for relapses to occur. And, in fact, they did occur in 42.5 percent of the group. It turned out that fat had a particularly devastating effect on the youngsters' relapse rate. For every 10 percent increase in energy intake that came from fat, there was a 56 percent increase in the children's risk of having a relapse. Saturated fats were the biggest driver of risk. When researchers look only at these fats, they discovered that the risk more than tripled. Examples of saturated fats include processed meats such as sausages, ham, and burgers, butter, hard cheeses, and whole milk. Vegetables had the opposite effect on risk, the researchers observed. Using a cup equivalent as a standardized measure, they learned that for every additional cup of vegetables the children ate, the risk of a relapse dropped in half. To exclude the possibility that other factors influenced the results, the team included information about age, sex, ethnicity, duration of disease, body mass index, treatment, and D-vitamin levels in their analyses. This did not influence the results. The team also looked at whether other food components, such as sugar, iron, fruit and fiber, would affect the risk of relapse. They did not find any links. Although the risk associations were strong, the researchers cautioned that the study's observational design meant that it was not able to prove that fat causes relapses. But there are several ways that fat could play a role in disease processes, they argued. For instance, high fat intake triggers the release of inflammation-promoting molecules. It also affectsf gut bacteria that are linked to immune processes. Vegetables lower the risk of inflammation and immune problems, the team said. In an accompanying editorial, Dr. Kathryn Fitzgerald of the Johns Hopkins School of Medicine said the study had important limitations. Researchers gathered information on the children's diet only in the week before they enrolled in the study. This might not adequately capture more long-term dietary patterns, she said. And fat is not simply fat, she pointed out, arguing that fish oil is believed to help MS patients. Although the California research offers insight, she called for long-term studies to define diet's role in MS.

Women with low levels of vitamin D in their blood are more likely to develop multiple sclerosis (MS) later in life, finds a large-scale study on women in Finland. The study, “25-Hydroxyvitamin D deficiency and risk of MS among women in the Finnish Maternity Cohort,” appeared in the journal…

Having a concussion when you’re 11 to 20 years old could increase your risk of developing multiple sclerosis later, a Swedish study suggests. The collaboration between Örebro University and Karolinska Institutet showed that a concussion in adolescence raised the risk of developing MS by 22 percent. Two or more concussions…

British military personnel are at significantly higher risk of dying from multiple sclerosis than people in other occupations, a study reports. University of Southampton researchers had done a previous study of mortality rates by occupation by checking records of residents of England and Wales. They noticed that the death rate among MS patients in the armed forces was much higher than that of people in other professions over three successive decades. MS has a genetic component but is also influenced by environmental factors, including vitamin D deficiency, smoking and certain viruses. Researchers wanted to learn why so many military people die of MS, and the causes. The team looked at the death records of men aged 20-74 between 1979 and 2010. They compared military people's MS-related mortality rates and death rates from all motor neuron diseases with those of other occupations. They also compared rates across social classes, which in the military presumably means lower-ranking enlisted people, higher-ranking enlisted people, and officers. They discovered that the MS-related mortality rate among military people was significantly higher than in other professions. The death rate from MS was also significantly higher than the rate from all motor neuron diseases in the armed forces. Interestingly, military people did not have a higher MS-related death rate when the team divided those in the study into three social classes or when they compared the armed forces mortality rate to those of similar occupations, such as police and fire services. The consistency of the findings, together with the high statistical significance observed, indicated that the results were not due to simple chance or a problem with the study method, the team said. They speculated that the higher military death rate could stem from the close proximity in which military personnel live and work, which could facilitate the transmission of infections that have the potential to cause MS. The results conflicted with those of a study that analyzed hospital admissions due to MS in a population of former military personnel. It reported no increased incidence of MS-related admissions in former military people, compared with non-military controls. Since such cohort studies are less prone to bias, the Southampton team called for more research on the topic.

The risk of people with multiple sclerosis developing cancer is higher if they have used immunosuppressants than if they haven’t, according to a study that followed more than 1,000 patients for a decade. The findings indicate that the often discussed association between MS and cancer may stem from older types of…

Coming down with the flu can provoke relapses in multiple sclerosis patients by activating glial cells that surround and protect nerve cells. In a study in mice, scientists found that activated glial cells increase the levels of a chemical messenger in the brain that, in turn, triggers an immune reaction and, potentially, autoimmune attacks. The flu is caused by the human influenza virus and, despite being unpleasant, usually resolves itself within days. However, for people with MS and other neurological conditions, the flu can lead to disease relapse. Researchers at the University of Illinois investigated what happens in the brain of MS patients during upper-respiratory viral infections, such as the flu. "We know that when MS patients get upper respiratory infections, they're at risk for relapse, but how that happens is not completely understood," Andrew Steelman, an assistant professor at the university and the study's senior author, said in a press release. "A huge question is what causes relapse, and why immune cells all of a sudden want to go to the brain. Why don't they go to the toe?" The team used a mouse model characterized by autoimmune responses within the brain and spinal cord — the type of deregulated immune responses seen in MS patients. Researchers infected the animals with a version of human influenza virus adapted to mice, and looked at changes that occurred in the animal’s central nervous system. While the virus was never detected in the animals' brains, upon infection some of the mice developed MS-like symptoms. "If you look at a population of MS patients that have symptoms of upper respiratory disease, between 27 and 42 percent will relapse within the first week or two," Steelman said. "That's actually the same incidence and timeframe we saw in our infected mice, although we thought it would be much higher given that most of the immune cells in this mouse strain are capable of attacking the brain." The team then investigated how a peripheral influenza infection could contribute to disease onset. They infected a wild-type (normal) strain of mice with the flu virus and looked at alterations in the brain and spinal cord. Scientists found that infection increased the activation of glial cells in the mice's brains. Moreover, it induced infiltration of several immune cells — T-cells, monocytes and neutrophils — into the brain within eight hours of infection. Overall, these findings suggest that the chemokine CXCL5 plays a key role in mediating an autoimmune attack in MS, and might be explored for therapeutic potential.

Last week saw much of the Pacific Northwest blanketed by smoke from wildfires in British Colombia. As I pondered the gray haze Thursday, I recalled a piece from a fellow columnist in June about air pollution and MS. In addition to MS, I also have asthma. Therefore, the health…

A variation in the NLRP1 gene is associated with multiple sclerosis that runs in families, Slovenian researchers report. Their study, “Identification of rare genetic variation of NLRP1 gene in familial multiple sclerosis,” was published in the journal Scientific Reports. The research was led by Dr. Borut Peterlin of Ljubljana University Medical Center's Clinical Institute of Medical Genetics. Scientists believe MS arises from a combination of a person's genetic background and the environment. Although previous studies have suggested that genes are behind MS that runs in families, researchers had yet to confirm that hypothesis. The Slovenian team wanted to identify any genes that were at play in both the MS and malignant melanoma that two siblings had. Although disease surveys indicate the two conditions can occur together, scientists had been unable to identify a shared cause for the two conditions. Interestingly, research has shown a link between a person's susceptibility to MM and a mutation of the NLRP1 gene. And recent studies have indicated that NLRP1 plays a role in the development of MM. The Slovenian team decided to evaluate the association between an NLRP1 mutation and multiple sclerosis in two groups. One consisted of 38 people with MS whose disease ran in the family. The other was 44 people with MS whose disease did not run in their family. Researchers used genomic, molecular biology and immunology measurements to decide whether there was a link between the mutation and MS. They found a connection between the mutation and MS that runs in families. The mutation affects the function of the protein the gene generates — a protein known to be involved in inflammatory processes. Researchers also found other NLRP1 mutations in patients with and without a family history of MS that they believe could be involved in the development of the disease. In addition, the team found evidence of a connection between MS associated with NLRP1 mutations and the development of MM. That evidence involved immune responses to the two conditions. Stimulating the production of immune-system components known as peripheral blood mononuclear cells, or PBMCs, triggered immune responses in MS patients with NLRP1 mutations. The responses included increased production of the pro-inflammatory cytokine IL-1β. Higher levels of that protein have been found in MM tissue. PBMCs include such immune cells as lymphocytes, monocytes, and macrophages. "IL-1β has been implicated in a variety of inflammatory and neurodegenerative processes occurring in MS,” the researchers wrote. Overall, the findings demonstrated an association between MS running in families and MM, they said. And the genetic link between the two may be the NLRP1 gene mutation, they added. The team said scientists might be able to develop a treatment for MS by finding a way to lower the increased production of IL-1β that NLRP1 mutations trigger.