Multiple Sclerosis Resource Centre
  • Home
  • About MS
  • MSRC Services
  • Get Involved
  • MS Research News
  • MSRC Groups
  • Useful Resources
  • Welcome To Josephs Court, MS Centre Of Excellence
  • Advertising
  • E-Newsletter
  • Contact Us
  • Cookie Policy
  • Investor in People
    You are here : Home » MS Research News » Environmental Factors And MS

    Environmental Factors And MS

    A A A
    [Print this page]

    Share |


    More news can be found in New Pathways Magazine, our bi-monthly publication, and also check daily at MSRC: Latest MS News.

    Excess mortality in MS largely from smoking

    Smoking And MSMuch of the early mortality seen in multiple sclerosis patients is related to their smoking habits, a researcher said here.

    In a prospectively followed cohort of nearly 900 MS patients, 68% of those who died in a 40-year period were current or former smokers, compared with 50% of surviving patients, according to Ali Manouchehrinia of the University of Nottingham in England.

    After adjusting for sex, age of MS onset, initial diagnosis (relapsing versus progressive MS), and use of disease-modifying drugs, the hazard ratio for death among ever-smokers versus lifetime nonsmokers was 2.13 (95% CI 1.26 to 3.61, P=0.005), he told attendees at the European Committee for Treatment and Research in Multiple Sclerosis annual meeting.

    The mortality rate in ever-smokers was 5.48 per 1,000 person-years, compared with 2.30 per 1,000 person-years among the lifetime nonsmokers in the cohort.

    Of the 66 patients in the cohort who died, 45 (68%) were smokers; 49% of the entire cohort were smokers.

    Manouchehrinia noted that deaths among never-smokers in the cohort still tended to be premature relative to the general population. But the difference was less than half that seen among patients with a smoking history.

    He also indicated that age of onset of significant disability was slightly younger in the ever- versus never-smokers, but the net result was that the never-smokers lived longer with disability, on average.

    Overall life expectancy among MS patients is about 5 years less than in other people, for reasons that are unclear. Smoking, however, is a strong epidemiological risk factor for development of MS, which also means that smokers are overrepresented in MS patients relative to the general population.

    Because smoking is itself associated with a substantial reduction in life expectancy, Manouchehrinia said, he and his colleagues sought to determine how much it may contribute to early mortality in MS patients.

    They examined data on 895 MS patients registered at Nottingham University Hospital who had been followed for up to 40 years after diagnosis. Smoking status was recorded in the data. A total of 66 patients in this cohort had died as of December 2011.

    Average age at death was 65, whereas the mean age of survivors as of December 2011 was 52. Decedents were also largely male (58%), whereas 72% of survivors were women.

    The distribution of diagnoses also differed significantly between decedents and survivors. Half the survivors had relapsing forms of the disease, compared with only 12% of patients who had died. Two-thirds of the decedents had secondary progressive disease at last follow-up, compared with 38% of the survivors.

    The differences largely reflected the older age of decedents, although Manouchehrinia noted that other research has suggested that disease progression is faster in smokers.

    Another difference between decedents and survivors was that 44% of the latter had received at least a year of disease-modifying therapy, compared with only 13% of those who died.

    Such disparities necessitated a multivariate analysis to assess the role of smoking in mortality. After adjusting for these factors, it remained the case that smoking approximately doubled the risk of death in the cohort, Manouchehrinia said.

    A Kaplan-Meier curve showed that, with disease duration of 45 years, the survival rate among ever-smokers was 50% compared with about 75% in lifetime nonsmokers.

    The researchers also calculated that, compared with life expectancy in the general population, a total of 1,779 years of life were lost prematurely in the cohort -- 62% of which were in ever-smokers.

    The study had no external funding.

    All authors declared they had no relevant financial interests.

    Primary source: European Committee for Treatment and Research in Multiple Sclerosis
    Source reference:
    Manouchehrinia A, et al "Smoking is a potentially modifiable risk factor for all causes of mortality in patients with multiple sclerosis" ECTRIMS 2012; Abstract 65.

    Source: Medpage Today © 2012 MedPage Today, LLC (15/10/12)

    A little dirt may be a good thing

    DirtSome experts say the body must learn to tolerate germs to protect itself from health problems.

    Good hygiene has saved millions of lives, protecting people from countless bacterial and viral infections, according to the U.S. Centers for Disease Control and Prevention.

    But there is growing concern that strict adherence to good hygiene, though a valuable means of protecting health, has left humans open to other forms of illness.

    Proponents of the "hygiene hypothesis" believe that reduced exposure to bacteria, viruses and parasites have impaired the immune system's ability to properly respond to environmental challenges.

    Researchers have identified the hygiene hypothesis as a possible cause or exacerbating factor in a number of illnesses and medical problems, said Dr. Graham A.W. Rook, a professor in the department of infection at the Centre for Clinical Microbiology at the University College London. These include:

    Severe allergic reactions.

    Gastrointestinal disorders, such as inflammatory bowel disease and Crohn's disease.

    Autoimmune disorders, such as type 1 diabetes and multiple sclerosis.

    "The evidence for all this is very, very powerful," Rook said. "It's very easy to show if you live on a farm or keep a dog, you're less likely to have these disorders. If you are the youngest child in a big family, you're less likely to have these disorders."

    The hygiene hypothesis has its roots in the theory of evolution, he said.

    "The bottom line is organisms that were present in mud, untreated water and feces were with us right from the start of humanity," Rook explained. Proponents of the hygiene hypothesis believe that the human body adapted to these organisms and began using them as a means of training the immune system.

    "What has happened over the course of evolution is, because these bugs had to be tolerated, they came to activate the tolerance of the immune system," Rook said. "They are the police force that keeps the immune system from becoming trigger-happy. Basically, the immune system is now attacking things it shouldn't be attacking."

    Dr. Mitchell H. Grayson, an associate professor of pediatrics at the Medical College of Wisconsin in Milwaukee, said that the hygiene hypothesis is most strongly linked to an increase in allergic diseases and asthma.

    "It's thought to have something to do with the way your immune system develops and is programmed," Grayson said. Bacteria in the environment teach an immune response to allergens that is more moderate and less severe. "In the absence of these bacteria, the immune system is thought to become more prone to allergic disease," he said.

    Rook said that other researchers have used the hygiene hypothesis to show that parasitic infections can aid in the treatment of such conditions as multiple sclerosis and Crohn's disease.

    Argentinean researchers, for instance, have shown that the presence of intestinal parasites can moderate the progression of multiple sclerosis. Follow-up studies indicated that, when people were treated for their parasitic infection, they had a relapse of MS.

    A research team at the University of Iowa found similar results related to Crohn's disease, showing that intestinal parasites helped regulate the autoimmune reaction that causes the intestinal disorder.

    On the flip side, such revelations carry risks. Doctors are concerned that some might use the hygiene hypothesis as an excuse to abandon good hygiene, causing a surge in diseases such as dysentery and cholera.

    "Public health and sanitation has been the single greatest improvement in our life expectancy," Grayson said. "I would not recommend living less cleanly."

    On the other hand, tolerance of a little dirt here and there won't hurt.

    "If your kids come back from the garden with a little mud on their hands, it's not a bad thing," Rook said. "They don't necessarily have to wash their hands before picking up a sandwich."

    In general, though, it's wise to maintain good overall hygiene, he said, and wait for the scientists to figure all this out. Larger studies are underway to determine the exact mechanism by which bacteria and parasites are causing the immune system to moderate its response, Rook said.

    "We need to figure out how to replace what is good from the microbiological environment while maintaining the advances of good hygiene so we can get the best of both worlds," Rook said.

    Source: Healthday Copyright © 2011 HealthDay (13/09/11)

    Link between environment and genetics in triggering MS found

    MS And GeneticsEnvironmental and inherited risk factors associated with multiple sclerosis – previously poorly understood and not known to be connected – converge to alter a critical cellular function linked to the chronic neurologic disease, researchers with the UC Irvine Multiple Sclerosis Research Center have discovered.

    The findings, which appear in the online, open-access journal Nature Communications, suggest that a unifying mechanism may be responsible for multiple sclerosis and point to therapies personalized according to genetic factors.

    "MS results from complex interactions between an individual's genetics and his or her environment," said study leader Dr. Michael Demetriou, a UCI neurologist and associate director of the Multiple Sclerosis Research Center. "Defining how these come together to induce the disease is critical for developing a cure. We've taken a giant first step toward understanding this."

    Using blood samples from about 13,000 people, Demetriou and colleagues identified the way environmental factors – including metabolism and vitamin D3, obtained through either sunlight exposure or diet – interact with four genes (interleukin-7 receptor-alpha, interleukin-2 receptor-alpha, MGAT1 and CTLA-4) to affect how specific sugars are added to proteins regulating the disease.

    Earlier work on mice by Demetriou revealed that changes in the addition of these specific sugars to proteins engender a spontaneous MS-like disease. They also found that N-acetylglucosamine (GlcNAc), a dietary supplement and simple sugar related to glucosamine, is able to suppress this process.

    The current research shows that both vitamin D3 and GlcNAc can reverse the effects of four human MS genetic factors and restore the normal addition of sugars to proteins. "This suggests that oral vitamin D3 and GlcNAc may serve as the first therapy for MS that directly targets an underlying defect promoting disease," Demetriou said.

    Virtually all proteins on the surface of cells, including immune and nervous system cells, are modified with complex sugars of variable lengths and composition. This adds information to proteins separate from that directly defined by the genome. The sugars interact with specific sugar-binding proteins on the cell, forming a molecular lattice that controls the clustering, signaling and surface expression of critical receptors and transporters, such as the T cell receptor and CTLA-4. Reducing sugar modification weakens the lattice and enhances growth and activity of immune system T cells in such a way that they increase neural degeneration – a hallmark of MS.

    Production of the complex sugars is regulated by both metabolic and enzymatic functions, the latter altered by genetic MS risk factors and vitamin D3. Demetriou pointed out that the MGAT1 genetic variant linked to MS increases or decreases the sugars attached to proteins depending on metabolism – one possible explanation for why people with the same genetic risk factor may or may not develop MS.

    These sugars have also been implicated in many other chronic diseases, such as diabetes and cancer, Demetriou added, so this work could open up entirely new areas of medicine.

    Source: Eureka Alert! (01/06/11)

    Possible cause and treatment for multiple sclerosis discovered

    MS DiagnosisResearchers have found evidence that an environmental pollutant may play an important role in causing multiple sclerosis and that a hypertension drug might be used to treat the disease.

    The toxin acrolein was elevated by about 60 percent in the spinal cord tissues of mice with a disease similar to multiple sclerosis, said Riyi Shi, a medical doctor and a professor of neuroscience and biomedical engineering in Purdue University's Department of Basic Medical Sciences, School of Veterinary Medicine, Center for Paralysis Research and Weldon School of Biomedical Engineering.

    The research results represent the first concrete laboratory evidence for a link between acrolein (pronounced a-KRO-le-an) and multiple sclerosis, he said.

    "Only recently have researchers started to understand the details about what acrolein does to the human body," Shi said. "We are studying its effects on the central nervous system, both in trauma and degenerative diseases such as multiple sclerosis."

    The compound is an environmental toxin found in air pollutants including tobacco smoke and auto exhaust. Acrolein also is produced within the body after nerve cells are damaged. Previous studies by this research team found that neuronal death caused by acrolein can be prevented by administering the drug hydralazine, an FDA-approved medication used to treat hypertension.

    The new findings show that hydralazine also delays onset of multiple sclerosis in mice and reduces the severity of symptoms by neutralizing acrolein.

    "The treatment did not cause any serious side effects in the mice," Shi said. "The dosage we used for hydralazine in animals is several times lower than the standard dosing for oral hydralazine in human pediatric patients. Therefore, considering the effectiveness of hydralazine at binding acrolein at such low concentrations, we expect that our study will lead to the development of new neuroprotective therapies for MS that could be rapidly translated into the clinic."

    The researchers also learned the specific chemical signature of the drug that binds to acrolein and neutralizes it, potentially making it possible to create synthetic alternatives with reduced side effects. The studies are detailed in a paper appearing online this month in the journal Neuroscience. The paper was written by doctoral students Gary Leung, Wenjing Sun and Lingxing Zheng; graduate research assistant Melissa Tully, who is an MD-Ph.D. student at Purdue and the Indiana University School of Medicine; postdoctoral researcher Sarah Brookes; and Shi.

    In multiple sclerosis, the myelin insulation surrounding nerve cells is destroyed and the nerve fibers themselves are damaged.

    "We think that acrolein is what degrades myelin, so if we can block that effect then we can delay the onset of MS and lessen the symptoms," Shi said.

    Acrolein induces the production of free radicals, compounds that cause additional injury to tissues after disease or physical trauma.

    "We've discovered that acrolein may play a very important role in free radical injury, particularly in multiple sclerosis," Shi said.

    The elevated acrolein levels in the MS mice were cut in half when treated with hydralazine. The drug represents a potential long-term therapy to slow the disease's progress.

    "To our knowledge, this is the first evidence that acrolein acts as a neurotoxin in MS and also the first time anyone has demonstrated hydralazine to be a neuroprotective drug," Shi said.

    Other researchers had previously shown that acrolein damages liver cells and that the damage can be alleviated by hydralazine, leading the Purdue researchers to study its possible effects on spinal cord tissues.

    Further research will be conducted, and Shi's group has identified other potential compounds for binding acrolein. The research team, in a possible future collaboration with the Indiana University School of Medicine, also is working to improve the sensitivity of detection methods to measure acrolein levels in people with multiple sclerosis.

    Source: Machines Like Us © Copyright MachinesLikeUs.com 2010 (24/11/10)

    Study to look at environmental factors, MS progression

    MS MRIA $634,000 grant from the Department of Defense is allowing researchers at the University at Buffalo to investigate a trio of environmental factors and their influence on the progression of multiple sclerosis.

    The two-year project, headed by Murali Ramanathan, PhD, tests the hypothesis that nicotine metabolism, the byproducts of vitamin D metabolism and increased levels of anti-Epstein-Barr virus (EBV) each interact with variations in specific genes to cause increased neurodegeneration and increased lesions in MS patients.

    Ramanathan is a professor of pharmaceutical sciences and neurology in the School of Pharmacy and Pharmaceutical Sciences and the School of Medicine and Biomedical Sciences, respectively.

    The study is a collaboration between the UB and investigators from Charles University in Prague, Czech Republic, and will be conducted on samples obtained at both universities' MS centers.

    The research aims to identify gene-environmental interactions between key molecules in the vitamin D pathway, anti-Epstein-Barr virus antibodies, cigarette smoking and key genetic variants that are implicated in conversion of patients with clinically isolated syndrome (CIS) to definite MS.

    They will assess the risk of developing clinically definite MS and the time to progression, as well as the neurodegeneration in the brain of MS patients, as measured by brain atrophy, and the extent of brain injury caused by lesions.

    "We will use a novel approach to measure the levels of vitamin D and its metabolites, EBV exposure and nicotine metabolites from cigarette smoking," says Ramanathan. "We have developed sensitive and selective measurements for key metabolites in the vitamin D and nicotine metabolism pathways using mass spectrometry, a method that has not been used previously to study vitamin D metabolism.

    The novel study design will include the genetic variations that were associated with the risk of developing MS, as well as genes that determine the levels and responses to environmental factors. MS patients will be divided into two equal groups: a training group that will be used to identify gene-environmental interactions, and a group that will be used to replicate the training group result.

    "Identifying gene-environmental interactions is critical for developing better strategies for slowing the progression of MS, because it could enable patients with preexisting genetic risk factors to reduce the rate of disease progression through lifestyle modification," Ramanathan says.

    The study results will identify the gene-environment interactions that promote disease progression in MS and facilitate the development of preventive and therapeutic interventions for MS that disrupt these interactions, notes Ramanathan.

    Bianca Weinstock-Guttman, MD, Robert Zivadinov, MD, PhD, and Jun Qu, PhD, all of UB, are study co-principal investigators. Dana Horakova, MD, PhD, and Eva Havrdova, MD, PhD, are collaborators at Charles University in Prague.

    Source: Medical News Today © 2010 MediLexicon International Ltd (23/09/10)

    Multiple Sclerosis activity changes with the seasons, research finds

    The SeasonsNew research shows that multiple sclerosis (MS) activity can increase during spring and summer months. The research is published in the August 31, 2010, issue of Neurology®, the medical journal of the American Academy of Neurology.

    "Our results showed that the appearance of lesions on brain scans was two to three times higher in the months of March to August, compared to other months of the year," said study author Dominik Meier, PhD, of Brigham and Women's Hospital in Boston and a member of the American Academy of Neurology.

    For the study, researchers compared MRI brain scans of 44 people taken from 1991 to 1993 to weather data from the same time period. Participants were between the ages of 25 and 52 with untreated MS. Each person had eight weekly scans, then eight scans every other week followed by six monthly check-ups, for an average of 22 scans per person.

    Weather information included daily temperature, solar radiation and precipitation measurements for the Boston area.

    After one year, 310 new lesions were found in 31 people. Thirteen people had no new lesions during the study. "Not only were more lesions found during the spring and summer seasons, our study also found that warmer temperatures and solar radiation were linked to disease activity," said Meier. There was no link found between precipitation and lesions.

    "This is an important study because it analyzes records from the early 1990's, before medications for relapsing MS were approved, so medicines likely could not affect the outcome. A study like this probably won't be able to be repeated," said Anne Cross, MD, with the Washington University School of Medicine in St. Louis, who wrote an editorial about the study. Cross is also a member of the American Academy of Neurology. "Future studies should further explore how and why environmental factors play a role in MS."

    One significant aspect of the research is that clinical trials often use MRI to assess the effectiveness of a drug and studies commonly last between 6 and 12 months. If the study ran from spring to winter, it might appear that lesions decreased due to drug effect but the cause might just be change of season. The opposite would occur if a study started in winter and lasted through the spring and summer.

    Source: ScienceDaily © 1995-2010 ScienceDaily LLC (31/08/10)

    MS study suggests key role of environmental factor in the disease

    Genes & MSScientists are reporting what they say is compelling evidence that some powerful non-heritable, environmental factor likely plays a key role in the development of multiple sclerosis.

    Their finding, the cover article in the April 29, 2010 issue of Nature, results from the most advanced genomic analysis ever conducted on identical, or "monozygote," twins where one sibling has multiple sclerosis and the other does not.

    "Even with the very high resolution at which we sequenced the genomes of our study participants, we did not find evidence for genetic, or epigenetic differences that explained why one sibling developed the disease and the other did not," says the lead author of the study, Sergio Baranzini, PhD, associate adjunct professor of neurology and a member of the Multiple Sclerosis Research Group at University of California, San Francisco.

    The finding does not mean that genes do not play a role in the disease. In cases where one identical twin has MS, there is a 30-percent increased risk that the identical sibling also will develop the disease. In cases where a non-identical twin or other sibling has the disease, there is an increased risk of nearly 5 percent. However, says Baranzini, while limitations of current technology or small study size may have caused the team to miss important genetic divergence between twins, they consider the findings significant.

    The study was the first to examine all three levels of a human genome at the same time, giving the first full picture of a living genome. The scientists examined the genome sequences of one MS-discordant identical twin pair and the messenger RNA transcriptome and epigenome sequences of CD4+ lympohoctyes from three MS-discordant identical twin pairs.

    As a probe of a human genome, the study was a tour de force. The MS genome was explored at a depth of 20-fold coverage. By comparison, the first two single human genomes ever published - those of biologist and entrepreneur Craig Venter, PhD, followed by Nobel laureate James Watson, PhD - were sequenced at a depth of 7 to 8 fold coverage. In addition, the study investigated the first female genomes, the first genomes of twins and the first autoimmune disease individual genome sequences.

    Source: Physorg.com © PhysOrg.com 2003-2010 (28/04/10)

    Cigarettes, not Swedish snuff linked to increased risk of Multiple Sclerosis

    Cigarette smoking and MSWhile smoking cigarettes appears to significantly increase a person's risk of developing multiple sclerosis, using Swedish snuff does not, according to a study published in the September 1, 2009, print issue of Neurology®, the medical journal of the American Academy of Neurology.

    "While tobacco cigarettes increased a person's risk of developing MS, our research found that using Swedish snuff was not associated with an elevated risk for MS," said study author Anna Hedström, MD, of the Swedish medical university Karolinska Institutet in Stockholm."These results could mean that nicotine is not the substance responsible for the increased risk of MS among smokers."

    The study involved 902 people diagnosed with MS and 1,855 people without MS in Sweden between the ages of 16 and 70. All participants answered a questionnaire about tobacco cigarettes and snuff use.

    The researchers found that in women who smoked, the risk for developing MS was nearly one and a half times higher than in women who did not smoke. In men, the risk was nearly two times higher in those who smoked compared to those who did not smoke. This was the case even in people who only smoked moderately.

    The risk remained high for up to five years after the participant stopped smoking and the risk climbed the more a person smoked. However, the study also found that people who used Swedish snuff for more than 15 years were 70 percent less likely to develop MS than those who had never used any type of tobacco. However, there was no significant effect of snuff-taking for less than 15 years, a period during which other adverse consequences of taking snuff, including head-and-neck cancer, would become evident.

    Swedish snuff differs from snuff commonly used in the United States in that it is typically a moist powder that usually does not result in a need for spitting.

    "Taking snuff, however, may have other harmful effects, and our findings should not be interpreted to mean that Swedish snuff is recommended to prevent disease," said Hedstrom. "More research is needed to better understand the mechanisms behind the findings. Theories are that smoking may raise the risk of MS by increasing the frequency and persistence of respiratory infections, or by causing autoimmune reactions in genetically susceptible people."

    The study was supported by The Swedish Medical Research Council, the Swedish Council for Working Life and Social Research, the European Union's Sixth Framework Program NeuroproMiSe, Bibbi and Niels Jensens Foundation, Montel Williams Foundation and the Söderberg Foundation.

    Source: Eureka Alert! (01/09/09)

    MS patients who smoke show more brain atrophy, more lesions, than MS nonsmokers

    Smoking and MS

    Persons with multiple sclerosis who smoked for a little as six months during their lifetime had more destruction of brain tissue and more brain atrophy than MS patients who never smoked, a study by neuroimaging specialists at the University at Buffalo has shown.

    Research published in the Aug. 18, 2009, issue of Neurology®, the medical journal of the American Academy of Neurology, showed that "ever-smokers" had more brain lesions and greater loss of brain volume, as well as higher scores on the Expanded Disability Status Scale (EDSS), than MS patients who had no history of smoking.

    The EDSS score is an average number derived from measures of various functions of the central nervous system. It is based on a scale from 0 to 10, with 10 representing greatest disability. Nonsmokers recorded an average EDSS score of 2.5, compared to 3.0 for ever-smokers.

    "Cigarette smoking is one of the most compelling environmental risk factors linked to the development and worsening of MS," said Robert Zivadinov, M.D., Ph.D., UB professor of neurology, director of the Buffalo Neuroimaging Analysis Center (BNAC) where the research was conducted and first author on the study.

    "The biological basis of the potential link between smoking and MS has not yet been fully elucidated," Zivadinov said. "In addition to nicotine, cigarette smoke contains hundreds of potentially toxic components, including tar, carbon monoxide and polycyclic aromatic hydrocarbons.

    "In MS patients, smoking was associated with higher increased lesion burden and greater brain atrophy. Our results indicate that a wide range of quantitative brain MRI markers are affected by smoking in MS patients."

    The study involved 368 consecutive patients who were seen at the Baird Multiple Sclerosis Center of the Jacobs Neurological Institute (JNI), UB's Department of Neurology, UB School of Medicine and Biomedical Sciences.

    Within the study cohort, 128 had a history of smoking: 96 were active smokers who had smoked more than 10 cigarettes-per-day in the three months prior to the study start and 32 were former smokers who had smoked cumulatively for at least six months sometime in the past. The remaining 240 participants were lifelong nonsmokers.

    Nearly 80 percent in both groups were female, and nearly 75 percent were diagnosed with progressive MS, characterised by a steadily increasing disability.

    All participants were evaluated by a clinician, were rated by disability using the EDSS scale and underwent a variety of high-resolution magnetic resonance imaging (MRI) scans conducted by MRI analysts who were blinded to the patient's clinical status and characteristics.

    Results showed that smokers with MS had a greater breakdown of the blood-brain barrier, had nearly 17 percent more brain lesions -- patches of inflammation in the sheath surrounding the nerve fibers that impair their function -- than nonsmokers with MS, and also had less brain volume. Smoking also was associated with increased physical disability, as measured by the EDSS score.

    Bianca Weinstock-Guttman, M.D., director of the Baird MS Center, UB associate professor of neurology and a principal co-author on the study, said: "The findings underscore the detrimental effect of smoking, providing a link between smoking and a more severe brain injury in MS patients.

    "Increased antismoking education in schools and more targeted smoking cessation programs for patients with MS should be encouraged further and supported."

    Murali Ramanathan, Ph.D., associate professor of pharmaceutical sciences in the UB School of Pharmacy and Pharmaceutical Sciences, is senior author on the study. Additional authors, all from UB, are Komal Hashmi, M.D., Nadir Abdelrahman, M.D., Milena Stosic, M.D., Michael G. Dwyer, Sara Hussein and Jackie Durfee.

    The research was funded by an independent grant from the BNAC, by the National Multiple Sclerosis Society and by a Pediatric MS Center of Excellence Center Grant. The Pediatric MS Center of Excellence is located in Women and Children's Hospital of Buffalo. The BNAC is located in Buffalo General Hospital. Both hospitals are part of Kaleida Health.

    Commenting on the findings, Helen Yates, Multiple Sclerosis Resource Centre Chief Executive said, “We have known for a very long time now that smoking cigarettes can have a huge impact on people’s health in a number of different ways.  This research seems to show that for people with MS, the impact is particularly detrimental in respect of this condition along with its negative impact on overall health”

    Source: University of Buffalo © 2009 University at Buffalo. (18/08/09)

    Young smokers increase risk for Multiple Sclerosis

    Smoking and MS

    People who start smoking before age 17 may increase their risk for developing multiple sclerosis (MS), according to a study released today that will be presented at the American Academy of Neurology's 61st Annual Meeting in Seattle, April 25 to May 2, 2009.

    The study involved 87 people with MS who were among more than 30,000 people in a larger study. The people with MS were divided into three groups: non-smokers, early smokers (smokers who began before age 17), and late smokers (those who started smoking at 17 or older), and matched by age, gender, and race to 435 people without MS.

    Early smokers were 2.7 times more likely to develop MS than nonsmokers. Late smokers did not have an increased risk for the disease. More than 32 percent of the MS patients were early smokers, compared to 19 percent of the people without MS.

    "Studies show that environmental factors play a prominent role in multiple sclerosis," said study author Joseph Finkelstein, MD, PhD, of Johns Hopkins University School of Medicine, in Baltimore, MD, which conducted the study in collaboration with Veterans Affairs MS Center for Excellence. "Early smoking is an environmental factor that can be avoided." (21/02/09)

    Environment may cause increase in Multiple Sclerosis among women only

    MS Brain Scan

    Gender has become a dominant factor in Multiple Sclerosis (MS) during the last decades. Already with a ratio of 3.2 to 1 MS is gradually changing into a disease predominantly among women. Since genetic factors can be ruled out as a cause of this gender related increase, scientific attention is on environmental factors that may increase MS risk in women exclusively. Most likely environmental factors include smoking, viral infections, Vitamin D deficiency, hygiene changes and dietary factors.

    Almost 400 MS scientists and clinicians from around the world gathered this week during a medical scientific conference on 'Multiple Sclerosis and Gender', organized by the independent European Charcot Foundation, to share and discuss their scientific views on the backgrounds of this major shift in gender ratio.

    "In due course the raised attention on gender related topics will undoubtedly lead to better results and questions regarding individualised MS treatment, both in women and men", professor O.R. Hommes, chairman of the European Charcot Foundation stated. "This conference has raised the simple question whether females with MS should be treated differently than males".

    One of the main focal points in the gender related approach is the effect of pregnancy on disease progression in MS. The disease practically disappears during the last trimester of pregnancy. Why is that and can we use our vast knowledge of natural female sex hormones, such as estriol, progesterone and prolactin, to develop new ways of treating women with MS? Several phase III clinical trials are already underway that will provide answers to this question by the end of 2009.

    Multiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system leading in time to severe disability. This chronic disease is affecting 70 to 200 per 100.000 persons in Europe.

    Source: Medical News Today © 2008 MediLexicon International Ltd (18/11/08)

    Activists applaud Congress move to slate military funds for multiple sclerosis research

    US Flag

    For the first time, Congress has approved spending Defense Department money to research a possible link between multiple sclerosis and military service -- which could help pinpoint the cause of a disease striking 400,000 Americans.

    The $5 million allocation will be awarded competitively to researchers.

    "We are very, very happy," said Shawn O'Neail, vice president of federal government relations for the National Multiple Sclerosis Society. "This was the result of a grassroots movement across the country."

    National and local MS activists credited a 2007 Courier-Journal story with helping drive that movement and leading to the federal money.

    After the article detailed the potential MS-military connection, the disease was listed last fall as a research area eligible for Defense Department medical funding. And veterans began sharing their stories with lawmakers.

    "When you did the story, it hit everywhere. Next thing you know, I'm testifying before Congress," said Bob Wolz, of Rineyville, Ky., a 43-year-old Gulf War veteran with MS featured in the article. "It's amazing what we were able to achieve in such a short amount of time. Just to know all these folks came together and stormed Capitol Hill is gratifying."

    He's one of a growing number of Persian Gulf War veterans who have developed the chronic neurological disease, which suggests a link to toxic substances, such as chemicals used in weapons or smoke from oil well fires.

    There's no known cause yet for MS, but experts suspect a genetic susceptibility, combined with some sort of trigger -- long thought to be an infectious agent such as a virus.

    The disease -- which affects an estimated 4,500 people in Kentucky and southeastern Indiana -- occurs when a fatty tissue called myelin, which helps nerve fibers conduct electrical impulses, is lost.

    "Gulf War data certainly increases one's concern that maybe there could be a toxic substance triggering MS," said Dr. John Richert, executive vice president for research and clinical programs for the MS Society.

    Finding a chemical trigger, he said, would be "the first solid evidence" that toxins play a role.

    Studies may reveal link
    The federally funded research will build upon recent studies hinting at a link between MS, military service and war.

    A Georgetown University study, led by Dr. Mitchell Wallin and published in the Annals of Neurology in 2003, found higher-than-normal MS rates among veterans who served from 1960 to 1994, which the study said "strongly imply a primary environmental factor in the cause or precipitation of this disease."

    Wallin identified more than 5,000 service-connected cases among veterans serving during those years.

    A 2005 study in the journal European Neurology showed that MS among Kuwaitis more than doubled between 1993 and 2000. And other studies, which looked more generally at the problems dubbed "Gulf War Syndrome," mention the possible dangers of oil-well smoke, vaccines and sarin from the destruction of weapons.

    Wolz, a former Army sergeant who also served in Operation Iraqi Freedom, believes his MS began during his tour of duty in 1990 and 1991.

    A decontamination specialist with a chemical unit, he was in Kuwait when the oil wells burned, and he said he believes chemical exposure, or possibly anthrax vaccinations, could have brought on his illness.

    During that tour, he suffered mysterious blackouts, and his left arm and leg got weaker and thinner. The problems continued at home, and doctors diagnosed him with MS in 2006.

    Cause drawing support
    Since being featured in The Courier-Journal in June 2007, Wolz has worked to bring attention and money to the cause. After getting a call from O'Neail of the MS Society, Wolz testified at a February 2008 briefing for congressional staffers, along with Georgetown's Wallin and a retired Army Medical Corps officer who also served in the first Gulf War and developed MS.

    In June, Wolz testified before the Senate Appropriations Committee Subcommittee on Defense.

    Meanwhile, MS activists, who began seeking grassroots support for MS-military research in 2006, got more than 100,000 signatures on a petition. Other groups eventually signed on to the effort, including the American Academy of Neurology, the Paralyzed Veterans of America and Disabled American Veterans.

    Wolz told the Senate panel in June that the stakes are high, the ramifications broad.

    "Every hour, someone is newly diagnosed with MS," he said, according to a transcript. "It is the most common neurological disease leading to disability in young adults." Wolz and Dave Autry, deputy national director of communications for Disabled American Veterans, said they were surprised that Congress approved the money in such a tight budget climate.

    "We've seen research money fall under the budget axe in the past," Autry said.

    But the funding was part of a bill passed by the Senate on Sept. 27 and signed into law three days later.

    Autry said he hopes the research yields findings that can protect future members of the military from getting MS.

    Wolz said he hopes it can help today's MS sufferers, too. For now, he gives himself shots of interferon beta-1 three times a week to fight the disease, which causes fatigue, sensitivity to hot and cold and cognitive problems that make him struggle for words.

    "If they find a trigger," he said, "they can start working on a cure."

    Source: Courier-Journal.com © Courier-Journal 2008 (20/10/08)

    High prevalence of multiple sclerosis in area investigated

    MS Brain

    Researchers at the University of Illinois College of Medicine at Rockford already know two of the communities in the area they will cover in a new study have a high prevalence of multiple sclerosis.

    Paw Paw and Morrison were included in a 2003 study by the college of five small communities where residents had expressed concerns about perceived high rates of multiple sclerosis and arterial lateral sclerosis. Results of that study, published in July, listed cases in the two communities and Lewistown, in Fulton County, as highly elevated.

    Cases in the other two communities — Savanna and DePue — were found not to be elevated.

    “The prevalence of MS nationally is about one-tenth of 1 percent of the population,” Joel Cowen, assistant dean for health systems research at the College of Medicine, said of the 2003 survey. “We were looking here at about two to three times that for our entire population.”

    The new study, which has been soliciting participation by MS patients, covers 13 northwestern Illinois counties to determine if those counties have a higher prevalence of multiple sclerosis than other areas of the state. 

    Cowen, who also will conduct the new study, said concerns about Paw Paw and Morrison laid the foundation for the 2003 study, financed by a $100,000 grant from the federal Agency for Toxic Substances and Disease Registry. The new study is financed by the state through an Excellence in Academic Medicine grant.

    Other conclusions of the 2003 study were:

    The prevalence for the five communities equaled 187 per 100,000 compared with a National Health Interview Survey for the nation of 85 per 100,000.

    The prevalence for women was especially high at 340 per 100,000 for the five communities combined.

    Eleven women had MS for every man, higher than the national rate of two to three for every man.

    Northern European ancestry appeared to play a role in the high levels.

    The 2003 study also attempted to measure whether there were environmental causes for the high number of multiple sclerosis cases, but Cowen said, “We could not prove that there was an environmental relationship. Of course, environmental risks are latent. They take decades, sometimes, to have an effect.”

    Source: rrstar.com © 2008 GateHouse Media, Inc.(07/10/08)

    US veterans' Multiple Sclerosis study awaits President's sign-off

    US FlagThe Veterans Benefits Improvement Act of 2008, now awaiting President Bush's signature, contains a provision to determine whether veterans of the Persian Gulf War in 1991 and of post-9/11 wars are at increased risk for multiple sclerosis.

    Senate Bill 3023 passed the House last month and was sent to the White House last Thursday. If passed, a wide ranging, comprehensive study of veterans of Desert Storm, and of those in current conflicts, would be conducted to examine incidents of multiple sclerosis and other neurological disorders. A final version would be due New Year's Eve, 2012.

    The multiple sclerosis proviso is especially significant to Desert Storm veterans, who seem to suffer disproportionatlely from a variety of neurological illnesses linked in part to exposure to various toxins during their service.

    The measure would direct the secretary of the Veterans Affairs Department to contract with the Institute of Medicine of the National Academies to study and identifying any increased risk of developing multiple sclerosis as a result of service in modern warfare after 1991.

    "Identify the incidence and prevalence of diagnosed neurological diseases, including multiple sclerosis, Parkinson's disease, and brain cancers, as well as central nervous system abnormalities that are difficult to precisely diagnose..." one element of the legislation says.

    The VA already has accepted service-connections for other neurological illnesses, notably brain cancer, fibromyalgia and ALS, better Known as Lou Gehrig's disease.

    U.S. Sen. Patty Murray, D-Wash., has taken up the cause of veterans with multiple sclerosis. We've been chronicling developments of Desert Storm's veterans with multiple sclerosis for some time now, including some who live in the Seattle area.

    Source: seattlepi.com ©1996-2007 Seattle Post-Intelligencer (07/10/08)

    Smoking is a risk factor for early conversion to clinically definite multiple sclerosis

    Cigarettes

    Background

    Cigarette smoking increases the risk for development of multiple sclerosis and modifies the clinical course of the disease. In this study, we determined whether smoking is a risk factor for early conversion to clinically definite multiple sclerosis after a clinically isolated syndrome.

    Methods

    We included 129 patients with a clinically isolated syndrome, disseminated white-matter lesions on brain magnetic resonance imaging, and positive oligoclonal bands in the cerebrospinal fluid. The patients' smoking status was obtained at the time of the clinically isolated syndrome.

    Results

    During a follow-up time of 36 months, 75% of smokers but only 51% of non-smokers developed clinically definite multiple sclerosis, and smokers had a significantly shorter time interval to their first relapse. The hazard ratio for progression to clinically definite multiple sclerosis was 1.8 (95% confidence interval, 1.2–2.8) for smokers compared with non-smokers (P = 0.008).

    Conclusions

    Smoking is associated with an increased risk for early conversion to clinically definite multiple sclerosis after a clinically isolated syndrome, and our results suggest that smoking is an independent but modifiable risk factor for disease progression of multiple sclerosis. Therefore, it should be considered in the counseling of patients with a clinically isolated syndrome.

    Source: Sage Journals Online © 2008 by SAGE Publications (26/08/08)

    Chronic barium intoxication disrupts sulphated proteoglycan synthesis: a hypothesis for the origins of multiple sclerosis
    High level contamination by natural and industrial sources of the alkali earth metal, barium (Ba) has been identified in the ecosystems/workplaces that are associated with high incidence clustering of multiple sclerosis (MS) and other neurodegenerative diseases such as the transmissible spongiform encephalopathies (TSEs) and amyotrophic lateral sclerosis (ALS).

    Analyses of ecosystems supporting the most renowned MS clusters in Saskatchewan, Sardinia, Massachusetts, Colorado, Guam, NE Scotland demonstrated consistently elevated levels of Ba in soils (mean: 1428 ppm) and vegetation (mean: 74 ppm) in relation to mean levels of 345 and 19 ppm recorded in MS-free regions adjoining. The high levels of Ba stemmed from local quarrying for Ba ores and/or use of Ba in paper/foundry/welding/textile/oil and gas well related industries, as well as from the use of Ba as an atmospheric aerosol spray for enhancing/refracting the signalling of radio/radar waves along military jet flight paths, missile test ranges, etc.

    It is proposed that chronic contamination of the biosystem with the reactive types of Ba salts can initiate the pathogenesis of MS; due to the conjugation of Ba with free sulphate, which subsequently deprives the endogenous sulphated proteoglycan molecules (heparan sulfates) of their sulphate co partner, thereby disrupting synthesis of S-proteoglycans and their crucial role in the fibroblast growth factor (FGF) signalling which induces oligodendrocyte progenitors to maintain the growth and structural integrity of the myelin sheath.

    Loss of S-proteoglycan activity explains other key facets of MS pathogenesis; such as the aggregation of platelets and the proliferation of superoxide generated oxidative stress. Ba intoxications disturb the sodium-potassium ion pump–another key feature of the MS profile. The co-clustering of various neurodegenerative diseases in these Ba-contaminated ecosystems suggests that the pathogenesis of all of these diseases could pivot upon a common disruption of the sulphated proteoglycan-growth factor mediated signalling systems.

    Individual genetics dictates which specific disease emerges at the end of the day.

    Purdey M.

    Source: Oregon Skywatch © 2008 Oregon Skywatch (16/06/08)

    Smoke exposure may increase the risk of multiple sclerosis.

    PURPOSE AND METHODS: To estimate the effect of exposure to smoking on the risk for multiple sclerosis (MS), we analyzed nicotine metabolite (cotinine) levels in biobank samples from 109 MS cases and 218 matched referents.

    RESULTS: Elevated cotinine levels, even modest elevations, were associated with an increased risk for MS (all other categories versus lowest: OR = 2.9; 95% CI: 1.3-6.3). A similar but non-significant risk increase was observed also in the small subset of individuals with samples collected before the onset of MS (all other categories versus lowest: OR = 2.4; 95% CI: 0.26-21). Elevated cotinine was associated with an increased risk for MS predominantly in women (all other categories versus lowest category: OR = 3.9; 95% CI: 1.3-12), whereas the risk increase in men was smaller and non-significant.

    DISCUSSION: Smoke exposure is associated with a higher risk for MS than previously estimated. There seems to be a threshold effect present in the lower range of cotinine in its relation to MS. Modestly elevated cotinine levels suggestive of passive smoking are associated with an increased risk for MS. Smoke exposure may explain the higher incidence of MS in women. These preliminary findings need to be confirmed in an expanded material of prospectively collected samples.

    Sundström P, Nyström L, Hallmans G.
    Department of Neurology, Umeå University Hospital, Umeå, Sweden. [email protected]

    Source: Pubmed 18474075 (22/05/08)

    Environmental factors linked to development of autoimmune diseases
    Scientists working at the MRC National Institute for Medical Research have shown that environmental factors can influence the development of autoimmune diseases like multiple sclerosis.

    A team led by Dr Brigitta Stockinger has identified a molecular mechanism that links a wide range of environmental factors to the autoimmune reactions in which immune system cells attack body tissue. The results are published online in Nature.

    The research focused on a protein called the aryl hydrocarbon receptor (AhR). Activation of the AhR causes enzymes to be produced that are involved in reducing the toxic effect of a wide range of chemicals on the human body. Many of these, such as dioxin, are generated in industrial processes. The research found that stimulation of AhR by environmental factors could be involved in development of autoimmune disease.

    The researchers looked at the effect that both AhR and environmental factors had on autoimmune disease in mice.

    Dr Stockinger said: ''Multiple factors can influence the development of autoimmune diseases, these include genetics, hormones, diet, the presence of infection or exposure to chemical and environmental irritants. Autoimmune diseases are becoming increasingly common in industrialised countries and it is likely that this is connected to environmental factors.''

    The AhR is present in a group of T helper cells called Th17 in both the mouse and human immune systems. T helper cells generate a response to infection by stimulating the immune cells that produce antibodies and those that destroy other infected cells.

    Under normal circumstances, Th17 cells are important in mounting an immune reaction to fungal and bacterial infection. Th17 cell activity is also the cause of some autoimmune diseases including multiple sclerosis and rheumatoid arthritis.

    The research found that if AhR is activated in mice while Th17 cells are developing, the proportion of Th17 cells present in the body increases and so the potential for the development of autoimmune disease is enhanced. The AhR is activated by environmental factors.

    Dr Stockinger explains: ''The AhR system can potentially react to an astounding range of factors, from environmental pollutants to particular foods or even hormone levels. So here we have identified a molecular mechanism that shows how such a wide range of environmental factors could be directly linked to the cells that cause autoimmune reactions.''

    In comparison, mice that lack AhR still develop Th17 cells and T helper cell responses but they don't have enhanced numbers of these cells. This suggests that AhR interaction with environmental factors leads to an increase in the number of Th17 cells and may contribute to the onset or development of autoimmune diseases in genetically susceptible individuals. In addition, the research showed that stimulation of AhR resulted in faster development of autoimmunity with greater severity. This means that environmental factors are interacting with genetic factors to generate a detrimental autoimmune reaction.

    Dr Stockinger concludes: ''The discovery that the stimulation of AhR by environmental pollutants can accelerate the development of autoimmune reactions and the severity of symptoms raises intriguing possibilities and warrants closer examination of a possible role of AhR in human autoimmune diseases."

    Source: News-Medical.net Copyright © 2008 News-Medical.Net(31/03/08)

    Congressional Briefing Examines Multiple Sclerosis Among Veterans
    Two U.S. veterans living with multiple sclerosis and a neurologist with the Veterans Affairs MS Center of Excellence testified at a briefing on Thursday, February 21, on Capitol Hill. Legislators and staff gathered to examine the increased prevalence of the disease among U.S. veterans and explore the need for increased federal investment in MS research.

    New evidence shows a potential link between the incidence of multiple sclerosis and combat service. A recent study in the Annals of Neurology identified 5,345 cases of MS among U.S. veterans that were deemed "service-connected." The National Multiple Sclerosis Society, in cooperation with Congressmen Russ Carnahan (MO) and Michael Burgess, M.D. (TX), co-chairs of the Congressional Multiple Sclerosis Caucus, hosted the briefing.

    Dr. Mitch Wallin, an Associate Professor of Neurology at Georgetown University School of Medicine and Associate Director of Clinical Care at the Department of Veterans Affairs MS Center of Excellence-East in Baltimore, shared his experience treating members of the U.S. military living the disease and his findings on the increased risk of MS among veterans.

    Dr. David Gustavison is a U.S Army Medical Corps veteran who served in the Gulf War and lives with MS. Dr. Gustavison shared his perspective as a medical doctor with a clear understanding of the disease.

    “I believe there is a relationship between military service and MS,” Dr. Gustavison said. “Myself and three other physicians in the same command were diagnosed with MS in approximately a two-year time period. Two of us were deployed to the Gulf. All three had the same pre-deployment vaccinations. And all three worked with the same command and visited the same installations. I have had symptoms of MS since 1994.”

    Bob Wolz also shared his story of life with multiple sclerosis. He is a U.S. Army veteran who served in the Gulf War and considers MS a lingering wound from his first tour of duty. “I was exposed to something,” Bob said.

    The National Multiple Sclerosis Society is pursuing a noncompetitive $15 million appropriation specifically for MS research in the Congressionally Directed Medical Research Programs (CDMRP) at the Department of Defense. That funding is allocated under the annual Defense appropriations bill.

    Source: I'm An MS Activist (26/02/08)

    Environmental factors and multiple sclerosis

    Abstract

    Studies in Canada have provided strong evidence that environmental factors act at a population level to influence the unusual geographical distribution of multiple sclerosis (MS). However, the available data accommodate more than one type of environmental effect.

    Migration studies show that changes to early environment can greatly affect risk, and there are recent indications that risk can be altered in situ. The rising incidence rates of MS in Canada implied by longitudinal increases in sex ratio place this effect in temporal context and narrow the candidates for mediating the effect of environment. Similarly, geographical patterns in Australia imply that modifiable environmental factors hold the key to preventing some 80% of cases.

    Genetic epidemiology provides overwhelming evidence that genetic background has an important complementary role. If genetic factors are held constant, the environment sets the disease threshold. Although these could be independent additive risk factors, it seems more likely that susceptibility is mediated by direct interactions between the environment and genes.

    Source: The Lancet Neurology Volume 7, Issue 3, March 2008, Pages 268-277 (12/02/08)

    Migration and multiple sclerosis: The French West Indies experience.

    The French West Indies (FWI), i.e., the islands of Martinique and Guadeloupe, have recently experienced the emergence of multiple sclerosis (MS).

    This epidemiological upheaval followed a return migration of the FWI population that had previously migrated to continental France.

    The prevalence MS was 14.8/10(5) (95% CI: 11.9-17.7) on Dec. 31, 1999 and its mean annual incidence was 1.4/10(5) (95% CI: 1.0-1.8) for the period July 1997 to June 2002.

    The prevalence of MS in Martinique, that received more return migration, is higher than that of Guadeloupe (21.0/10(5)vs. 8.5/10(5)).

    This emergence of MS has been accompanied also by an inversion of its clinical spectrum, with recurrent neuromyelitis optica accounting for only 17.8% of cases.

    The standardized ratio of the incidence of MS among migrants is 1.71 (95% CI: 1.19-2.38; P<0.01) and if migration to continental France occurred before the age of 15 it is 4.05 (95% CI: 2.17-6.83; P<0.0001).

    According to recent data, a drastic reduction in exposure to sunlight and to intestinal parasites during childhood, found preferentially among migrants, are possible environmental factors responsible for this emergence.

    Cabre P. Service de Neurologie, CHU Fort de France, Hôpital Pierre Zobda Quitman, BP 97261, Fort de France, Martinique, France.

    Source: J Neurol Sci. 2007 Nov 15;262(1-2):117-21. (30/10/07

    Increased risk of multiple sclerosis in medical staff

    Background:

    Multiple sclerosis (MS) has been hypothesized to be due to an immune response leading to CNS demyelination. Yet it's not known for certain what triggers the immune processes responsible for MS development. Other explanations than genetic/immunity are discussed to express MS in nonfamilial clusters, predominantly by means of infectious agents.

    Method:

    We used the MS database of the Isfahan MS Society (IMSS), which includes almost all MS patients in Isfahan province. It contains 1809 [persons with]definite MS, diagnosed from April 2003 to January 2007 according to McDonald's criteria.

    Results:

    Surprisingly, 105 MS patients were working as medical personnel. These included 35 physicians, 27 nurses and 24 midwives. In Isfahan, an approximate number of 9200 are working in health care organizations. They include about 5000, 3000, 1200 physicians, nurses and midwives, respectively.

    Isfahan is considered to be a medium-high-risk area for MS, with a prevalence of 43.8/100000. The MS prevalence among medical staff is significantly higher than for the normal population (P value < 0.001).

    Within medical personnel, midwives were considerably more at risk of developing MS than physicians and nurses. 2% of all midwives living in Isfahan, compared to 0.9% and 0.7% of nurses and physicians respectively, developed MS. But the difference between MS prevalence in physicians and nurses was not significant (P value=0.32).

    Conclusion:

    The huge MS rate among medical personnel suggests alternative risk factors for MS development. Recently, infectious agents have received considerable attention as an alternative cause of multiple sclerosis.

    Pathogens such as Chlamydia, Human T leukemia Virus 1, herpes virus and Epstein-Barr virus are suspected of causing MS development, and they support the role of a sexually transmitted agent in MS development.

    Medical personnel are generally more exposed to infectious agents, but members of different occupations such as physicians, nurses or midwives are in contact with different amounts and types of infectious agents. So, we suggest that midwives have more potential for developing multiple sclerosis due to their contact with sexually transmitted pathogenic agents.

    V. Davoudi, K. Keyhanian, M. Amin, M. Etemadifar, A. Maghzi, K. Basiri (Isfahan, IR)

    Source: ECTRIMS conference in Prague, October 11-14, 2007 (22/10/07)

    Cigarette Smoking May Accelerate Disability In Those With MS
    People with multiple sclerosis who smoke risk increasing the amount of brain tissue shrinkage, a consequence of MS, and the subsequent severity of their disease, new research conducted at the Buffalo Neuroimaging Analysis Center (BNAC) at the University at Buffalo has shown.

    The results are based on magnetic resonance images (MRIs) of smokers and nonsmokers in 368 MS patients treated in UB's Jacobs Neurological Institute, the university's Department of Neurology in its School of Medicine and Biomedical Sciences.

    "Cigarette smoke has many properties that are toxic to the central nervous system, and cigarette smoking has been linked to higher susceptibility and risk of progressive multiple sclerosis," said Robert Zivadinov, M.D., Ph.D., UB professor of neurology, director of the BNAC and first author on the study.

    "Interactions between cigarette smoking and genetic and immunologic factors may point to mechanisms in disease pathogenesis. No previous studies have investigated differences in MRI characteristics between MS cigarette smokers and MS nonsmokers," he said.

    The study included patients from the three most common forms of MS: 253 had relapsing-remitting MS -- acute attacks with full or partial recovery; nine had primary-progressive MS -- steady worsening from onset; and 90 had secondary-progressive MS, characterized by occasional attacks and sustained progression. Another 16 participants had experienced their first MS onset.

    Patients ranged in age from 35-55 years, and had been living with MS for an average of 13 years. The Expanded Disability Status Scale (EDSS), an average number derived from measures of various functions of the central nervous system based on scales ranging from 0 to 10, was 3.1. The higher the number, the greater the disability.

    Within the study cohort, 128 had a history of smoking: 96 were active smokers who had smoked more than 10 cigarettes-per-day in the three months prior to the study start, and 32 were former smokers who had smoked cumulatively for at least 6 months sometime in the past. The remaining 240 participants had no active smoking exposure.

    The average smoking duration was 17.6 years and the average number of cigarettes smoked per day was 17. There were no significant differences between smokers and nonsmokers based on age, disease duration, disease course and total lifetime use of disease-modifying drugs.

    Analysis and comparison of the MRIs from smokers and nonsmokers showed that the smokers had significantly higher disability scores and lower brain volume than the nonsmokers. There also was a significant relationship between a higher number of packs-per-day smoked and lower volume of the neocortex, the portion of the cerebral cortex that serves as the center of higher mental functions for humans.

    There were no significant differences in any of the clinical findings between active and former smokers.

    "Smoking appears to influence the severity of MS and to accelerate brain atrophy and the disruption of the blood-brain barrier in MS patients," said Zivadinov. "MS patients should be counseled to stop smoking, or at least to cut down so they can preserve as much brain function as possible."

    Results of the research were presented Oct. 13, 2007 at the 23rd Congress of the European Committee for the Treatment and Research in Multiple Sclerosis in Prague, Czech Republic.

    Source: University at Buffalo.(15/10/07)

    Cigarette smoking and progression in multiple sclerosis
    Objective: To investigate the influence of cigarette smoking on progression and disability accumulation in multiple sclerosis (MS).

    Methods: Information on past and present smoking of 364 patients with MS was obtained through a structured questionnaire survey. We used Kaplan-Meier analyses and Cox regression models to evaluate the influence of smoking on the development and age at onset of secondary progression, on the age at onset of progression in patients with primary progressive MS, and on the time from disease onset to Expanded Disability Status Scale (EDSS) scores 4.0 and 6.0 in all patients. We also investigated the correlation between smoked pack-years and EDSS scores and the rate of progression as measured with the Multiple Sclerosis Severity Score.

    Results: We found no significant associations between cigarette smoking and any of the used measures.

    Conclusion: Our data suggest that cigarette smoking has no influence on disease progression or accumulation of disability in multiple sclerosis.

    Marcus Koch, MD, Annemarie van Harten, Maarten Uyttenboogaart, MD and Jacques De Keyser, PhD

    From the Department of Neurology, University Medical Center Groningen, University of Groningen, The Netherlands.

    Source: NEUROLOGY 2007;69:1515-1520 © 2007 American Academy of Neurology (09/10/07)

    Hygiene hypothesis: Innate immunity, malaria and multiple sclerosis

    Summary

    The establishment of new hygienic conditions plays a role in the appearance of autoimmunity in “westernalised” countries. Consistently, but still unconvincingly, several epidemiological and immunogenetic evidences link the disappearance of malaria with the increase of multiple sclerosis (MS) in Sardinia, insular Italy.

    To this purpose, we have made an attempt to build a relationship between malaria disappearance and MS under the light of the hygiene hypothesis. This relationship has taken into account the MS frequency increase soon after malaria eradication in Sardinia, the present malaria endemism in Africa, the innate immune system activity here represented by Chitotriosidase (Chit), an hydrolytic enzyme produced by macrophages, and an unproductive polymorphism of Chit gene (CHIT1) as a measure of the genetic weight of Plasmodium-related immunity in these populations.

    Data were derived from both experimental results specifically designed for this study and other data obtained from the available literature. The experimental and the hystorical–epidemiological findings concur to indicate that whilst in Africa CHIT1 mutation is rare and MS incidence is very low due to unmodified parasitic influence and hygienic conditions, in Sardinia a relationships between CHIT1 mutation, plasma Chit activity and MS prevalence rate is detected, even to a higher extent compared to Sicily, area at former lower rate of malaria endemy.

    Upon such a basis, we have found convincing argumentations that, at least in part, MS has increased over the last four decades in Sardinia also because of the eradication of malaria, 50 years ago. This infectious disease that run for centuries in Sardinia, besides well documented enzyme deficiencies and red cell pathologies, have left an abnormal macrophage reactivity against Plasmodium falciparum. As a result, some Sardinian individuals secrete abnormally high levels of mediators of the innate immunity, relics of former protective anti-malaria infection, in response to new environmental factors.

    Therefore, MS, an immune-conditioned pathology of the central nervous system has been subject to an unexplained epidemiological increase in the last few decades in Sardinia because cells of the innate immune system, immuno-genetically selected over the centuries in response to widespread P. falciparum malaria, have kept the tendency to over-respond to triggering factors even after the disappearance of malaria. This hypothesis may have an influence in re-directing clinicians toward a innate immunity-based rather than an antigen specific-based new MS therapies.

    Stefano Sotgiuaa, Andrea Angiusbb, Ashton Embryc, Giulio Rosatiad and Salvatore Musumecid,e

    aInstitute of Clinical Neurology, University of Sassari, Viale San Pietro, 10, 07100 Sassari, Italy bInstitute of Population Genetics, National Research Council, (CNR), Alghero, Italy cDirect-MS, Calgary, Canada dDepartment of Pharmacology, Gynecology-Obstetrics, Pediatrics, University of Sassari, Italy eInstitute of Biomolecular Chemistry, CNR, Li Punti (SS), Italy

    Source: ScienceDirect Copyright © 2007 Elsevier B.V. All rights reserved (24/09/07)

    Multiple Sclerosis Rates Elevated in Kuwait 1993-2000

    Epidemiology of multiple sclerosis in Kuwait: new trends in incidence and prevalence.

    The epidemiology of multiple sclerosis (MS) is undergoing dramatic changes; MS is occurring with increased frequency in many parts of the world. In this retrospective study, we examined the changes in incidence and prevalence of MS in Kuwait in the period between 1993 and 2000.

    We analysed the records of patients with clinically defined and laboratory supported MS. The total incidence rate increased from 1.05/100,000 population in 1993 to 2.62/100,000 in 2000. The increased incidence of MS was most pronounced among Kuwaiti women (from 2.26/100,000 in 1993 to 7.79/100,000 in 2000. The total prevalence rate increased from 6.68/100,000 in 1993 to 14.77/100,000 in 2000. It was much higher for Kuwaitis (31.15/100,000), as compared to non-Kuwaitis (5.55/ 100,000), in a complete reversal of the pattern observed before 1990.

    The prevalence was also higher among Kuwaiti women (35.54/100,000), as compared with Kuwaiti men (26.65/100,000). In conclusion, the incidence and prevalence of MS in Kuwait has increased between the early and late 1990s with no signs of leveling off. In a geographic area that was previously associated with low prevalence, local environmental factors may be responsible for these dramatic changes.

    Alshubaili AF, Alramzy K, Ayyad YM, Gerish Y.
    Department of Neurology, Ibn Sina Hospital, Safat, Kuwait.

    Source: Veterans Today © 2007 The Veterans Today Network - All Rights Reserved (26/08/07)

    NARCOMS Report-Recent Research Findings

    Ruth Ann Marrie, MD, PhD-Mellen Center for MS Treatment and Research, Cleveland Clinic Foundation-CMSC/NARCOMS Research Fellow; Tuula Tyry, PhD, MAED-NARCOMS Program and Editorial Manager-Barrow Neurological Institute, Phoenix, Arizona

    Introduction
    The Consortium of Multiple Sclerosis Centers (CMSC) started the NARCOMS project in 1993 to aid multiple sclerosis (MS) research. More than 32,000 persons have enrolled in the NARCOMS Registry since 1996, when enrollment first opened. Participants are from the United States, Canada, and over 50 other countries around the world. After ten years of work, the value of the NARCOMS project is being demonstrated with a growing number of publications and presentations. We are very pleased to share some of the more recent research findings with you.

    Environmental Factors
    Three NARCOMS presentations at recent national meetings focused on environmental factors (such as sunlight exposure) in MS. Previous studies suggested a seasonal pattern to MS births (James, 1995; Willer et al., 2005). These studies found a higher fraction of MS births in the late spring implying that the pregnancy was occurring over months of low sunlight exposure, and a lower fraction of births occur in early winter following pregnancies that take place over high sunlight periods (James, 1995; Willer et al., 2005). We examined season of birth among 10,247 American NARCOMS participants, born in the Northern United States. Unlike other studies, we did not find a seasonal pattern to MS births. The greatest number of births was in September (933) and the fewest were in February (746); this difference was not meaningful (Figure 1).

    We did find, however, that NARCOMS participants are more likely to be born in northern latitudes than expected. About 29% of the US population was born north of 42 degrees latitude. More than 40% of NARCOMS participants were born north of 42 degrees latitude (Figure 2). This finding is consistent with previous migration studies; that is, studies of persons who move between areas with differing risks of MS. Prior studies of persons moving between the northern and southern parts of the US suggested that exposures during early life affect the risk of developing MS ( Detels et al., 1978). Factors being studied include infections, sunlight, vitamin D, and diet (Detels).

    A Canadian study suggested that the ratio of women to men with MS is changing (Orton et al., 2006). We looked at the female/male ratio among NARCOMS participants according to the year of diagnosis, and the age of MS onset. The ratio of women to men with MS was two to one in 1960, but increased to about four to one by 2000. This suggests that more women than men are developing MS. Smoking was examined as a potential factor, but did not explain the changes over time. More research is needed to find out why, but changing environmental factors are suspected to play a role. Possible factors could be lifestyle factors, workplace exposures, changes in diet or weight gain, and hormone therapy.

    Comorbidity and Lifestyle Factors
    Three NARCOMS presentations focused on co-existing health conditions and lifestyle factors in MS. In the Fall 2006 questionnaire, more than three-quarters of participants had a co-existing health condition. The most common conditions reported were high blood pressure, high cholesterol, and arthritis. These conditions are also common in the general population.

    Many participants reported that they currently smoked, or smoked in the past; 55% had ever smoked. More NARCOMS participants have ever smoked than persons of the same age in the general population (Figure 3). Several studies suggested that smoking is a risk factor for MS; our findings would be consistent with that hypothesis (Hernan, Olek, & Ascherio, 2001; Riise, Nortvedt, & Ascherio, 2003). One study suggested that smoking negatively affects disability in MS (Hernan et al., 2005). The high frequency of smoking among NARCOMS participants suggests that further research is needed about smoking and its effects on MS.

    We also examined physical activity. Physical inactivity increases the risk of heart disease, obesity, osteoporosis (thinning of the bones), and other health problems. NARCOMS participants reported low levels of physical activity during leisure time. Only a quarter of participants reported moderate or heavy leisure time activity. This is similar to the activity level reported in the general US population, but is less than recommended. The Centers for Disease Control recommends thirty (30) minutes of moderate physical activity on most days of the week. A regular exercise program can decrease MS-related fatigue and improve walking ability (Mostert & Kesselring, 2002; Oken et al., 2004; Romberg et al., 2004). Participants who had low levels of activity reported more fatigue and trouble walking than participants who were more active.

    Overall, these findings suggest that patients with MS often have more than one health condition. Patients may need help with quitting smoking, and finding ways to exercise despite disability and fatigue. More research is needed about co-existing health conditions and lifestyle factors in MS.

    Summary and Conclusions
    MS is a complex disease to understand, and there are many important questions yet to answer. NARCOMS Registry participants make an invaluable contribution to MS research. We truly appreciate your past and future contributions to the Registry.

    References
    Detels, R., Visscher B. R., Haile, R. W., Malmgren, R. M., Dudley, J. P., & Coulson, A. H. (1978). Multiple sclerosis and age a migration. American Journal of Epidemiology, 108, 386-393.

    Hernan, M. A., Jick, S. S., Logroscino, G., Olek, M. J., Ascherio, A., & Jick, H. (2005). Cigarette smoking and the progression of multiple sclerosis. Brain, 128, 1461-1465.

    Hernan, M. A., Olek, M. J., & Ascherio, A. (2001). Cigarette smoking and incidence of multiple sclerosis. American Journal of Epidemiology, 154, 69-74.

    James, W. H. (1995). Season of birth in multiple sclerosis. Acta Neurologica Scandinavica, 92, 430.

    Mostert, S., & Kesselring, J. (2002). Effects of a short-term exercise training program on aerobic fitness, fatigue, health perception and activity level of subjects with multiple sclerosis. Multiple Sclerosis, 8, 161-168.

    Oken, B. S., Kishiyama, S., Zajdel, D., Bourdette, D., Carlsen, J., Haas, M., et al. (2004). Randomized controlled trial of yoga and exercise in multiple sclerosis. Neurology, 62, 2058-2064.

    Orton, S. M., Herrera, B. M., Yee, I. M., Valdar, W., Ramagopalan, S. V., Sadovnick, A. D., et al. (2006). Sex ratio of multiple sclerosis in Canada: A longitudinal study. Lancet Neurology, 5, 932-936.

    Riise, T., Nortvedt, M. W., & Ascherio, A. (2003). Smoking is a risk factor for multiple sclerosis. Neurology, 61, 1122-1124.

    Romberg, A., Virtanen, A., Ruutiainen, J., Aunola, S., Karppi, S.L., Vaara, M., et al. (2004). Effects of a 6-month exercise program on patients with multiple sclerosis: A randomized study. Neurology, 63(11), 2034-2038.

    Willer, C. J., Dyment, D. A., Sadovnick, A. D., Rothwell, P. M., Murray, T. J., & Ebers, G. C. Canadian Collaborative Study Group. (2005). Timing of birth and risk of multiple sclerosis: Population based study. British Medical Journal, 330 (7483), 120.

    Source: United Spinal Association (18/08/07)

    Group eyes possible link between MS, Gulf War

    The National Multiple Sclerosis Society is keeping an eye on military veterans, especially those who served in the first Persian Gulf War and have since been diagnosed with the debilitating neurological disease.

    "There appears to be an increased risk of MS in combat vets," said Shawn O'Neail, the society's vice president for federal government relations. "Are Gulf War veterans at an increased risk of developing MS? We have a long way to go to say that comfortably."

    But they want to find out.

    The strongest evidence comes from a 2005 European Neurology study showing that from 1993 to 2000 - the years following the first Gulf War - the rate of MS among Kuwaitis more than doubled. "In a geographic area that was previously associated with low prevalence, local environmental factors may be responsible for these dramatic changes," the study said.

    If Gulf War vets do have an increased risk, it could lead researchers to a specific environmental trigger for the incurable disease. Finding a trigger could lead to better treatment and "dare I say, a cure," according to O'Neail.

    The society, with help from a nationwide grass-roots effort, lobbied Congress this year to include MS in the Congressionally Directed Medical Research Program, which is administered by the Defense Department.

    Included in the 2008 Defense Department budget - scheduled to go before the House Appropriations Committee on Monday - is a request for $15 million worth of MS research.

    While diseases studied in the program don't necessarily have a connection to military service, the society never pursued getting MS included before because "it never really made sense to us," O'Neail said. "It makes sense now."

    More than 25,000 veterans -from all wars - have been diagnosed with MS, O'Neail said. More than 5,000 of those cases have been classified "service connected" by the Department of Veterans Affairs. The society knows of at least 500 veterans with MS who served in the first Gulf War.

    But both the society and a Washington-based advocacy group - Veterans of Modern Warfare - believe that number could be much higher. Some vets "are being diagnosed with these very broad syndromes and (the VA) is not exploring it with MRIs and the proper testing" for MS, O'Neail said.

    The symptoms for Gulf War illness and MS can be similar, said Julie Mock, a Gulf War veteran with MS who runs Veterans of Modern Warfare. "There's quite a crossover and reason enough to believe these people ought to be tested," Mock said. "Err on the side of the veteran."

    Also, not every veteran with MS qualifies for service-connected disability. Veterans have to be diagnosed with MS within seven years of leaving the military to get the benefits, though legislation is pending in the Senate that would cut the time restriction.

    If the research is funded, the MS society would like to see the money earmarked for "research that will explore the potential connection between combat service and increased risk of developing MS," O'Neail said.

    The Hampton Roads chapter of the MS society isn't aware of any local Gulf War veterans living with the illness.

    "It's a very personal illness," said Shannon Rice, director of community development for the Hampton Roads chapter of the National MS Society. "People who are newly diagnosed - and we define newly diagnosed as within two years - don't always reach out to call us first."

    Rice estimates that there are 5,000 people in Hampton Roads and 10,000 in the state living with MS. Only 2,600 have become "clients" of the local chapter.

    If an environmental trigger was found, it would be a huge breakthrough for the entire MS community.

    "People who don't have MS get up in the morning and start walking around and don't even think about it," said Tom O'Donnell, a Coast Guard veteran living with MS in Gloucester. "I have to concentrate on every step I take."

    "We need this funding in the worst kind of way," said Buddy Hayes, the reigning Ms. Wheelchair Virginia. Hayes, a 49-year-old Chesapeake woman who served in the Army in the 1970s, was diagnosed with MS in 2003, after she lost the use of her legs.

    "If anybody thinks we don't need the funding, I've got two old, clunker wheelchairs in the garage. They can come and take them and see what it's like for one day."

    Source: dailypress.com Copyright © 2007, Newport News, Va., Daily Press (22/07/07)

    DePue mayor skeptical about MS study
    Mayor Don Bosnich was disappointed with the results of a recent study that found only one case of multiple sclerosis in DePue.

    "I don't think it's an accurate depiction of the situation," Bosnich said after a meeting Thursday to discuss the study results. The study suggested no link between MS and the environmental hazards from a zinc smelting facility that closed in 1987 in DePue, a Bureau County village.

    The study was conducted by the Health Systems Research, a part of the University of Illinois College of Medicine in Rockford. The study measured the prevalence of MS, a chronic disease that steadily weakens the central nervous system, in five Illinois towns: DePue, Lewistown, Morrison, Paw Paw and Savanna.

    Joel Cowen, principal investigator for the project, said at Thursday's meeting that 37 cases of MS were found in those areas, where residents had environmental concerns.

    Out of those 37, one was from DePue and nine were from Lewistown, the Fulton County seat. Lewistown has about 2,500 residents, and some have concerns about an elevated level of MS from water contamination.

    Sewer sludge from Chicago was shipped to Lewistown between 1972 and 1987 to be used as fertilizer. The EPA has been monitoring soil and water quality in Lewistown for 30 years.

    Cowen said the study found the number of cases of MS in Lewistown was higher than the national average, but no association could be made with health conditions resulting from environmental factors.

    The same was said for all five towns included in the study, including Paw Paw, which received fertilizer from the DePue zinc-smelting site. Paw Paw, a Lee County town of about 850, had three cases in the study.

    The rate of MS in DePue, a town of about 1,600 people, was actually below the national average.

    Cowen said the study did suggest MS is more common among individuals of northern European ancestry, such as Dutch or German. The disease is also more likely to be found in the northern region of the U.S.

    Also, the study found a high proportion of females had the disease, as 34 of the 37 cases were women.

    Bosnich said the DePue study was too limiting. Only people who lived there from 1998 to 2002 could participate.

    "There are people who lived in DePue in their early 20s and 30s," Bosnich said. "They've since moved out. Yet, they grew up in this town and suffered through the zinc smelting and they were left out of this study. To me, it seems very flawed and not realistic."

    Cowen said researchers had to follow strict guidelines set by the Centers for Disease Control and Prevention that limited the areas to be studied.

    Project coordinator Barbara Sjostrom said 22 cases were reported in LaSalle County and 13 in Bureau County, nine of whom were Spring Valley residents. The Spring Valley statistics could not be used for this study.

    Cowen said he hoped to receive another grant, which would allow the group to include a greater research area, including all of LaSalle and Bureau counties.

    Bosnich said he grew up with several people who had MS in DePue, and other people at the meeting said they knew of at least six people from the town who suffered from the disease.

    "I know there are more cases," Bosnich said. "This is upsetting to me."

    Source: PJStar.com © 2007 PEORIA JOURNAL STAR, INC (19/01/07)

    Results to be announced of the prevalence of Multiple Sclerosis in Lewistown, other towns
    Lewiston — The results of a study concerning the prevalence of multiple sclerosis in Lewistown and four other small Illinois communities are to be announced at 7 p.m. Monday, Jan. 22, at the Park District Building, 1203 N. Broadway, Lewistown.

    The previous meeting to present the results was canceled by the Dec. 2 snowstorm.

    Responding to citizen concerns about a perceived high number multiple sclerosis (MS) cases in small Illinois communities, Health Systems Research of the University of Illinois College of Medicine at Rockford, submitted a grant to study the prevalence of the disease in DePue, Lewistown, Morrison, Paw Paw, and Savanna.

    The grant was received in October 2002 from the Agency for Toxic Substances and Disease Registry (ATSDR), a division of the Centers for Disease Control and Prevention (CDC), funded as one of five areas in the nation to study MS and ALS (Lou Gehrig's Disease).

    That study, which sought to determine local rates and compare them to national levels, has now been completed and the results will be announced in a series of presentations in the five study communities.

    Health Systems Research sought to find all individuals with MS and ALS who lived in the zip code areas of the communities from 1998 to 2002. Self-identifying individuals then completed information on their medical, residential, and occupational history and gave permission for their medical records to be reviewed to verify the diagnosis.

    Source: The Daily Ledger Copyright © 2006 GateHouse Media, Inc. Some Rights Reserved. (15/01/07)

    Study seeks to link MS and climate
    A major New Zealand study into multiple sclerosis (MS) may confirm suspicions that South Islanders are more likely to get the disease than those from the North.

    The degenerative disease, which affects an estimated 3500 New Zealanders, appears to strike more often in populations further from the equator, with Scotland reporting one of the highest rates of MS in the world.

    A New Zealand study has found people from Otago were 2 1/2 times as likely to get the disease as those from the Bay of Plenty.

    For the first time, a major research team is attempting to survey every MS patient in New Zealand.

    As well as questions about income and lifestyle, it will examine where each person has lived throughout their life. It will also study racial origins.

     Internationally the disease is more prevalent amongst Caucasians. It is uncommon in Asians and believed to be rare in Maori and Pacific Islanders.

    Christchurch neurologist Bruce Taylor said the study was the largest of its kind in the world.

    "It is a very, very exciting study and a really important study for New Zealand."

    Taylor said the cause of the regional variation was unclear. One theory was that a lack of sunshine during winter caused a critical shortage of vitamin D in developing immune cells affecting their regulation. It appeared most important in the first 15 years of life.

    MS also had a genetic component and was typically triggered in those susceptible by an "insult to their immune system", such as an infectious illness.

    Multiple sclerosis patients have scars in their brain and spinal cord, where bouts of inflammation have healed. The inflammation damages the nerve fibres leading to symptoms such as fatigue, poor balance or blurred vision. The inflammation heals spontaneously allowing symptoms to ease or disappear.

    It can also leave permanent impairment, increasing with each episode. There is no cure, though MS is rarely fatal and most people with MS have a near-normal life expectancy.

    The use of MRI had drastically reduced the time to diagnosis from as long as 10 years after the first symptoms appeared to about one year.

    Taylor and his team want to contact all those with a confirmed diagnosis of MS by Census Day, March 7, 2006. This would allow the MS population to be directly compared with that of the general population.

    Taylor hoped data collection in the $400,000 study would be complete by July next year.

    Amongst those who have completed a questionnaire is former Press journalist John Brown, diagnosed with MS in 1966, aged 28.

    The doctors told his wife he would be in a wheelchair within two years and dead by the age of 40 and advised her not to tell him.

    He said it was "quite some time" before he finally learnt what was causing tingling in his arms and legs and split vision.

    Despite increasing difficulty walking, he did not become totally dependent on a wheelchair for 30 years and was able to continue working as a journalist and travelled extensively.

    Episodes of serious depression, sometimes leading to hospitalisation, were a symptom of his MS and were more incapacitating than paralysis, said Brown.

    Now 68, and paralysed from the waist down, Brown remained articulate and active, travelling daily from his Sydenham home by powered wheelchair. Last month he had a feature published in The Press about the poor pay for personal caregivers.

    Source: The Press, New Zealand

    A question of degrees
    Multiple sclerosis is being mapped in Australia as a key part of global research into the disease.

    The battle to conquer the debilitating auto-immune disease known as multiple sclerosis is a multidisciplinary, international, 24-hour-a-day enterprise.

    As scientists in Australia are putting on their PJs, others in Los Angeles are throwing down their first coffee and getting ready for work. Researchers in Stockholm are already at the lab and teams in Britain are knuckling down to the afternoon shift.

    These researchers come from fields as diverse as genetics, proteomics, epidemiology, pharmacology, neurobiology and stem cell research, and they're making progress - though it probably seems too slow for those who have MS, including 16,000 people in Australia.

    Among the more promising developments is Tysabri, a drug from the US that in clinical trials overseas and in Australia has been shown to markedly slow the progress of the relapsing-remitting form of MS.

    Tysabri works by preventing inflammatory white blood cells from leaving the blood stream and entering the central nervous system, where they attack (and scar, hence the term "sclerosis") the protective coating on the nerve fibres.

    "Tysabri appears to be a quantum leap better than interferon beta [the best treatment available at present]," says Dr David Booth, a research scientist at Westmead's Millennium Institute working on the genetics of MS.

    Tysabri became available in the US in 2004 but was withdrawn last year after two drug-trial participants died from a rare neurological condition. (For perspective, more than 8000 people had by that time been taking the drug, according to Biogen, its manufacturer.)

    The drug is being re-evaluated by the US Federal Drug Administration and Biogen expects to hear about its findings by the end of the month.

    However, it needs to proceed through the Therapeutic Goods Administration and the Pharmaceutical Benefits Scheme before introduction into Australia, and that may take between 18 months and three years, says Jeremy Wright, the executive director of Multiple Sclerosis Research Australia.

    Australia's contribution to MS research is relatively small in terms of numbers of scientists but "punches well above its weight", Wright says. "We are connected to probably all the major [MS] studies [in the world] in one way or another."

    One of the more notable Australian research projects is the Ausimmune study.

    With bases in Brisbane, Newcastle, Geelong and Tasmania, its aim is to examine the influence of environmental factors on immunity and how the occurrence of auto-immune diseases, including MS, varies according to latitude.

    Australia's long north-to-south reach and relatively homogenous population make it an excellent laboratory in which to study the effects of environmental factors, such as climate, on health, the study's organisers say.

    Our nationwide health-care system makes it easier to be systematic about finding people with early symptoms of auto-immune disease who might take part.

    For the study, people who have had a "first demyelinating event" - an early symptom that may be a forerunner of MS - and other people from the general community who act as controls are asked a comprehensive range of questions about their life and medical history.

    The data from both sets of people are then compared to see if there are any significant differences between the two.

    Preliminary data already shows that "for every degree of latitude you go south, there is a 6 to 8 per cent increase in the number of first demyelinating events", says Dr Robyn Lucas, an epidemiologist at the National Centre for Epidemiology and Population Health, which is running the study.

    "Then you have to wonder what things are different by latitude. Hobart is colder, wetter and has less sun than Queensland. You probably get more infections in colder climates you probably eat a different diet. So there are lots of things that vary by latitude and we are trying to look at all of those."

    Booth says: "A dominant theory [about the link between latitude and MS] is that you get more vitamin D where you get more sunlight, and this has an impact on the immune system."

    This is the basis for Booth's ongoing studies into vitamin D receptor genes and MS.

    The Ausimmune team hopes to publish its findings by the end of next year, Lucas says, and "the best hope we have is to find some clear-cut environmental risk factors that are amenable to some sort of intervention".

    Wright says there is already a prevention strategy being considered that will involve providing pregnant women from families with a strong genetic link to MS with more vitamin D during their pregnancy.

    There is little doubt among the scientific community, however, that MS involves a number of genetic and environmental factors, so no single discovery is likely to provide a definitive answer.

    Source: The Sydney Morning Herald Copyright © 2006.

    Investigation of a Cluster of Multiple Sclerosis in Two Elementary School Cohorts
    Abstract

    The authors investigated a cluster of multiple sclerosis (MS) among people who had attended two elementary schools in El Paso, Texas, from 1948 through 1970. The community was concerned about the possibility of childhood exposure to heavy metals from a large nearby smelter because historical environmental and biological sampling data demonstrated the potential for study cohort members to have been exposed to heavy metals during their pre-adolescent years.

    One cohort had no reported cases of MS. In the second cohort, 22 members self-reported a diagnosis of MS, and 16 of these cases were confirmed as MS by an independent board-certified neurologist. The crude MS prevalence estimate was 411 per 100,000 (95 percent confidence interval [CI] = 197-603). Prevalence estimates from four different populations were used for calculation of standardised morbidity ratios (SMRs). At the extremes, the study cohort represents a deficit of cases (SMR= 0.9; 95 percent CI = 0.51-1.44) or a fourfold excess (SMR = 4.0; 95 percent CI = 2.29-6.5).

    Introduction

    Multiple sclerosis (MS) is a demyelinating disease of the central nervous system and one of the most common causes of neurological disability in young adults (Institute of Medicine, 2001). Although the number of people with MS in the United States is unknown, it is estimated that 250,000 to 350,000 people are affected by this disease (Anderson et al., 1992). MS differentially affects women, people 30-60 years of age, and Caucasians. Although MS can be diagnosed at any age, the diagnosis is unusual before adolescence, rises steadily from the teens to age 35, and then declines gradually thereafter (Hauser, 1994). Disease progression varies but typically involves a series of remissions and relapses that become more severe over time (Williamson & Henry, 2004).

    In December 1994, the Texas Department of Health (TDH) was asked to investigate an apparent "cluster" of 15 individuals with multiple sclerosis who had grown up in the Kern Place-Mission Hills neighborhood in El Paso, Texas, from the 1940s through the 1960s. If a national prevalence estimate of 102 per 100,000 was applied to the estimated 3,100 residents in the area, approximately three cases of MS would have been expected (Minden, Marder, Harrold, & Dor, 1993). Although most investigations of non-infectious-disease clusters are resource intensive and rarely contribute to an understanding of the etiology of the disease-particularly in the case of cluster concerns that center on past environmental exposures-the El Paso cluster request had a number of unique features that prompted TDH to pursue the cluster investigation (Williamson & Henry, 2004). These features included the magnitude of the apparent excess of MS in the community, the possibility that historical environmental and biologic sampling data could be located and linked to individual members of the study cohort, and a unique opportunity to examine a retrospective cohort in which the purported exposure preceded diagnosis of the disease.

    Although the etiology of MS is unknown, a number of environmental exposures have been investigated as possible risk factors, including infectious agents, solvents, trauma, pets, and diet, but the findings have not been consistent (Kahana, 2000; Marrie et al., 2000; Minden et al., 1993; Sorensen & Ransohoff, 1998; Weinshenker, 1996). One current theory suggests that environmental exposures to a genetically susceptible individual may trigger the development of MS, with some studies suggesting that the critical time period for environmental exposures is before puberty (Hogancamp, Rodriquez, & Weinshenker, 1997; Kahana, 2000; Kurtzke, 2000; Kurtzke & Heltberg, 2001; Marrie et al., 2000; Poser, 1994; Sadovnick, Dyment, & Ebers, 1997). Exposure to metals has also been considered as an etiologic factor in several studies, including cluster investigations, although no definitive conclusions or associations have been found (Ingalls, 1986; Ingalls, 1989; Irvine, Schiefer, & Hader, 1988; Schiffer, Weitkamp, Ford, & Hall, 1994; Stein, Schiffer, Hall, & Young, 1987).

    Concerns raised by community residents in the initial stages of the El Paso cluster investigation included the possible impact of a local metals smelter, particularly impacts from past operations at the facility and neighborhood environmental contamination. The smelter operated in El Paso from 1887 to 1999, processing primarily lead, copper, cadmium, and zinc, and is located approximately one mile from the Kern Place-Mission Hills neighborhood. It is also located adjacent to a second neighborhood of concern, Smeltertown. Unlike the Kern Place-Mission Hills neighborhood, which was predominantly non-Hispanic white and middle to upper middle class during the 1950s and 1960s, Smeltertown was predominantly Hispanic and primarily comprised families of the smelter workers (Agency for Toxic Substances and Disease Registry [ATSDR], 2002).

    Extensive environmental and biological sampling was conducted in El Paso in the early 1970s by local, state, and federal environmental and public health agencies. The sampling demonstrated the potential for study cohort members to have been exposed to heavy metals during their pre-adolescent years. Historical sampling efforts documented high levels of metals from the facility's air emissions (ATSDR, 1996), as well as elevated levels of lead, zinc, arsenic, and cadmium in the soil.

    Blood lead surveys conducted by the local health department and the Centers for Disease Control and Prevention (CDC) in the early 1970s showed that many children living in the study neighborhoods were exposed to harmful levels of lead. In one study, 53 percent of children one to nine years of age living within one mile of the smelter had blood lead levels of 40 micrograms per deciliter of blood ^g/dL or greater. The authors concluded that paniculate lead in dust and air accounted for most of the lead exposure in El Paso children and that the smelter was the principal source of the lead (Landrigan et al., 1975). Smeltertown was raised in the early 1970s because of the heavy-metals contamination in the soil (ATSDR, 2002).

    In 1997, TDH received funding from ATSDR, a federal public health agency, to examine the prevalence of MS in El Paso. Early in the initial stages of the cluster investigation, three women who had been diagnosed with MS provided childhood hair samples for metals analysis. The hair samples consisted of ponytails collected in 1956 and 1962 from two women when they were 12 years old and a braid taken from a third woman when she was six years old. Analyses showed elevated levels of lead and mercury in all three samples and elevated levels of zinc and copper in the hair taken from both of the 12-year-olds (ATSDR, 2002). These early findings led the investigators to search for the original blood lead studies and environmental sampling data collected in the early 1970s.

    The goals of our study were to:

    • 1) Determine the number of individuals with MS in the Kern Place-Mission Hills cohort,
    • 2) Evaluate the feasibility of determining the number of individuals with MS in the Smeltertown cohort,
    • 3) Compare the prevalence of MS in the two cohorts to national estimates to determine if there was an excess, and
    • 4) Evaluate the feasibility of obtaining historical environmental and biological sampling data and matching the data with study cohort members.

    Methods

    A complete census of the children residing in El Paso neighborhoods from the 1940s through the 1960s was not available. Attendance at the local public elementary schools that served the two neighborhoods of concern was used as a surrogate for residence. The Mesita Elementary School served the Kern Place-Mission Hills neighborhood, and Smeltertown children attended the E.B. Jones Elementary School. A retrospective study design was used to investigate the prevalence of MS among students who had attended the elementary schools at any time from 1948 through 1970. This time frame was selected because of the expected availability of school records, the feasibility of tracing the cohort, and the natural history of the disease. The CDC Institutional Review Board approved the study protocol.

    The cohort was identified primarily through school district records for the local elementary schools, with school record information used to trace cohort members and obtain current addresses. Multiple tracing techniques were used to locate current addresses for the eligible cohort, including Web-based commercial databases, review of state drivers' license records, inquiries made to El Paso high school alumni associations, inquiries made to the TDH Bureau of Vital Statistics, public meetings, and referrals from classmates. A one-page, self-administered questionnaire that solicited basic demographic data, information on school attendance, and MS status was mailed to each former student for whom an address could be located. TDH staff re-contacted individuals reporting a diagnosis of MS to obtain authorisation to review medical records related to their MS diagnosis and a signed release-of-information form before requesting medical records.

    An independent board-certified neurologist reviewed copies of medical records and classified individuals according to case status using the Poser criteria (Poser et al., 1983). Individuals were classified into one of four diagnostic categories: definite, probable, possible, or not MS. Standardised morbidity ratios (SMRs) were used to determine if an excess of MS was present in the cohort. An SMR is the ratio of observed number of cases to expected number of cases. The observed number of cases is the number of individuals with the disease under consideration, and the expected number of cases is calculated on the basis of the disease occurrence in a reference population, usually a registry or surveillance system (Greenland & Rothman, 1998). The expected number of cases is the number of cases that would be present in the study cohort if those individuals developed the disease at the same rate as the people in the reference population.

    For our study, the observed value used in the SMR calculation was the number of neurologist-confirmed cases of definite and probable MS in the study cohort. Because no population-based registries or ongoing surveillance efforts exist for MS in the United States, prevalence estimates from four sources were used to calculate the expected number of cases:

    • 1) the Mayo Clinic in Olmstead County, Minnesota (Wynn, Rodriguez, O'Fallen, & Kurland, 1990);
    • 2) the 1989- 1994 National Health Interview Survey (Noonan, Kathman, & White, 2002);
    • 3) a 1976 survey of physicians and hospitals by the National Institute of Neurological Disorders and Stroke National Survey (Baum & Rothschild, 1981); and
    • 4) a recently completed pilot MS surveillance project conducted by TDH in 19 Texas counties (ATSDR, 2004).

    To calculate the SMR, one divides the observed number of cases by the expected number of cases. A ratio of 1.0 indicates that the number of cases observed in the population being evaluated is equal to the number of cases expected on the basis of the rate of disease in the reference population. A ratio greater than 1.0 indicates that more cases occurred than expected, and a ratio less than 1.0 indicates that fewer cases occurred than expected. The SMRs were tested for significant deviation from 1.00 with Fisher's exact test and exact confidence intervals for the Poisson variate.

    An attempt was also made to locate the original environmental and biological sampling data from the early 1970s. The authors of the published articles that summarised the studies were contacted (CDC, 1973; Landrigan et al., 1975; Morse, Landrigan, Rosenblum, Hubert, & Housworth, 1979; Rosenblum, Shoults, & Candelaria, 1976). The investigators also examined hard copies of files from the El Paso City-County Health and Environmental District dating back to the late 1960s and early 1970s.

    Results

    A total of 5,272 students were identified as having attended the two public elementary schools from 1948 through 1970. The Mesita cohort had 3,891 students, and the E.B. Jones cohort had 1,384 students. Three students attended both schools during this time period. Table 1 provides basic demographic information about the elementary school cohorts and the survey respondents. The proportion of women was slightly higher among the survey respondents than in the two school cohorts, and the survey respondents also spent more years at the elementary schools.

    The racial and ethnic distribution of the survey respondents could not be compared with that of the entire cohort because neither race nor ethnicity was recorded on the original school records. A current address or confirmation of death was obtained for one third of the cohort (n = 1,680, or 32 percent). Of the Mesita elementary school students for whom a current address was available (n = 1,248), 54 percent returned a completed questionnaire (n = 677). Of the E.B. Jones elementary school students for whom a current address was available (n = 432), 29 percent returned a completed questionnaire (n = 125).

    No cases of MS were reported from the E.B. Jones Elementary School cohort. Twenty-two people in the Mesita cohort self-reported a diagnosis of MS (Table 2). Two people self-reported MS but declined to participate in the case confirmation portion of the study. Definite or probable MS was confirmed by an independent neurologist in a total of 16 individuals. Based on the 16 confirmed definite and probable cases, the crude MS prevalence estimate for the Mesita school cohort was 411 per 100,000 (95 percent CI = 197- 603 per 100,000). All 16 individuals classified their race/ ethnicity as non-Hispanic white, and all were between 46 and 59 years of age.

    Table 3 illustrates the wide range of risk estimates for the Mesita cohort that follow from use of the four comparison prevalence estimates. At the extremes, if prevalence estimates from Olmstead County, Minnesota, are used, the 16 cases of MS reported for the study cohort would represent a deficit of cases (SMR = 0.9; 95 percent CI = 0.51-1.44). If recently obtained Texas MS surveillance data are used as the baseline comparison prevalence, however, students in the El Paso Mesita elementary school cohort have four times the risk of developing MS (SMR = 4.0; 95 percent CI = 2.29- 6.5).

    Historical environmental and blood lead data were located in the course of the study. The samples had been collected in 1972, however, after the end of the study period. The environmental data, primarily from analyses of heavy metals in soil and dust, did indicate the potential for residences surrounding the elementary school to have been exposed to heavy metals. Blood lead surveys indicated that children living in the study neighborhood in the early 1970s were exposed to harmful levels of lead. The environmental and biological data could not, however, be matched to cohort individuals because the identifying information was limited.

    Three women with confirmed diagnoses of MS who had attended the elementary school during the study period provided TDH with childhood hair samples that were tested for heavy metals as a part of the study reported here. The samples were hair of a 12-year-old girl from 1956, the braid of a six-year-old girl from 1959, and the ponytail of a 12-year-old girl from 1962. All three samples showed elevated levels of lead (146.1 [mu]g/g, 42 [mu]g/g, and 49.3 [mu]g/ g respectively; normal range = 5-29 [mu]g/g) and mercury (27 [mu]g/ g, 1.6 [mu]g/g, and 2.1 [mu]g/g respectively; normal range = 0.4- 1.2 [mu]g/g). The samples from both 12-year-old girls showed elevated concentrations of zinc (330 [mu]g/g and 250 [mu]g/g; normal range = 130-220 [mu]g/g) and copper (320 [mu]g/g and 240 [mu]g/g; normal range = 5-46 [mu]g/g), and the sample from the six-year-old showed an elevated concentration of arsenic (8.46 [mu]g/g; normal range < 4 [mu]g/g) (ATSDR, 2002). The source of the metals found in the hair samples, however, could not be determined with certainty (Landrigan et al., 1975).

    Discussion

    This paper illustrates a number of the challenges faced by public health agencies tasked with addressing reported clusters of MS or other neurologic diseases for which little or no epidemiologic information is available. The most basic challenge was the lack of MS data available for Texas during the initial stages of the investigation. In most cluster investigations, a population-based registry or surveillance system would have been able to quickly identify cases in the geographic area and time period of interest. An existing Texas surveillance system would have been able to provide comparison prevalence estimates based on a uniform case definition that were timely and specific to the state, as well as sex and age-specific estimates.

    The prevalence estimates for the Mesita cohort presented in this paper are likely underestimates since there may be additional MS cases among the 67 percent of the Mesita school cohort who could not be located and surveyed during the course of the study.

    The excess of MS reported for the Mesita cohort versus no cases reported for the E.B. Jones cohort may represent a true difference in the disease experience of the two cohorts, or it could be due to the lack of participation by the former E.B. Jones school students. A lack of trust in government and perceived lack of benefit may have been contributing factors in the low participation rate. Many members of the E.B. Jones cohort were either part of the original childhood lead studies conducted in the 1970s or had family or friends who participated. Several study participants raised concerns about being used as study subjects again and a perceived lack of government response to the environmental concerns raised in the 1970s. Issues related to availability and access to medical care for the E.B. Jones cohort may also have played a role in the different MS prevalences in the two cohorts.

    Conclusions

    Although the El Paso MS cluster investigation had some unique study features, it shares many attributes with the host of MS cluster studies conducted over the past several decades. These studies often involve resource-intensive case-finding efforts, lack of region-specific comparison estimates, a wide range of etiologic hypotheses, and a frustrated community at the end of the investigation. Most of the cluster investigations generally leave more questions than answers, particularly those that demonstrate an excess of MS in a community. The number of cases in typical community cluster investigations, including this one, is too small to allow for a meaningful examination of potential etiologies.

    Local, state, and federal public health agencies around the United States are receiving ever-increasing numbers of MS inquiries, and expectation is growing among the public that these concerns will be taken seriously and addressed in a timely manner. Lessons learned over the past decades from cancer and birth defect cluster concerns and disease surveillance for these conditions can be applied to MS and other neurological diseases.

    The need to begin to plan and implement MS surveillance strategies that are able not only to assist states with cluster investigations, but also to provide the much-needed descriptive epidemiological basis from which we can pursue additional etiologic studies to define specific risk factors. In addition to surveillance, innovative strategies are needed to address ongoing community concerns about MS clusters. ATSDR has taken the lead in developing a large-scale, multisite case control study. This study will be able to examine a number of risk factors for MS, including heavy metals and the role of gene-environment interactions. Texas, Missouri, and Ohio will be participating in the case control study.

    Acknowledgements:

    The authors would like to thank the study participants who have been diagnosed with multiple sclerosis and who shared their experiences. We also acknowledge the participation and support of the El Paso City-County Health and Environmental District and the Region 10 director and staff who contributed to the study. The investigation was funded with a grant from the Agency for Toxic Substances and Disease Registry (Grant Number U50/ATU602898-12) and conducted with support from the Texas Tech Health Sciences Center Department of Neuropsychiatry.

    REFERENCES

    Agency for Toxic Substances and Disease Registry. (1996). Public health consultation multiple sclerosis cluster in El Paso. El Paso, TX: Author.

    Agency for Toxic Substances and Disease Registry. (2002). El Paso multiple sclerosis cluster investigation. El Paso, TX: Author.

    Agency for Toxic Substances and Disease Registry. (2004). Multiple sclerosis pilot surveillance in 19 Texas Counties. Lubbock, TX: Author.

    Anderson, D.W., Ellenberg, J.H., Leventhal, C.M., Reingold, S.C., Rodriguez, M., & Silberberg, D.H. (1992). Revised estimate of the prevalence of multiple sclerosis in the United States. Annals of Neurology, 31 (3), 333-336.

    Baum, H.M., & Rothschild, B.B. (1981). The incidence and prevalence of reported multiple sclerosis. Annals of Neurology, 10, 420-428.

    Centers for Disease Control and Prevention. (1973). Epidemiologic notes and reports: Human lead absorption-Texas. Morbidity and Mortality Weefety Review, 22, 405-407.

    Greenland, S., & Rothman, K.J. (1998). Introduction to categorical statistics. In K.J. Rothman & S. Greenland (Eds.), Modem Epidemiology (pp. 234-235). Philadelphia: Lippincott-Raven Publishers.

    Hauser, S. (1994). Multiple sclerosis and other demyelinating diseases. In K.J. Isselbacher & J.B. Martin (Eds.), Harrisons Principles of Internal Medicine (pp. 2289-2295). New York: McGraw- Hill.

    Hogancamp, WE., Rodriguez, M., & Weinshenker, B.C. (1997). The epidemiology of multiple sclerosis. Mayo Clinic Proceedings, 72, 871- 878.

    Ingalls, T.H. (1986). Endemic clustering of multiple sclerosis in time and place, 1934-1984. Confirmation of a hypothesis. American Journal of Forensic Medicine & Pathology, 7(1), 3-8.

    Ingalls, T. (1989) Clustering of multiple sclerosis in Galion, Ohio, 1982-1985. American Journal of Forensic Medicine & Pathology, 10(3), 213-215.

    Institute of Medicine. (2001). Multiple sclerosis: Current status and strategies for the future. Washington, DC: Author.

    Irvine, D., Schiefer, H., & Hader, W.J. (1988). Geotoxicology of multiple sclerosis: The Henribourg, Saskatchewan, cluster focus. II. The soil. Science of the Total Environment, 77(2-3), 175-188.

    Kahana, E. (2000). Epidemiologic studies of multiple sclerosis: A review. Biomedidne and Phamacotherapy, 54(2), 100-102.

    Kurtzke, J.F. (2000) Multiple sclerosis in time and space- Geographic clues to cause. Journal of Neurovirology, 6(S2), S134- S140.

    Kurtzke, J.E, & Heltberg, A. (2001) Multiple sclerosis in the Faroe Islands: An epitome. Journal of Clinical Epidemiology, 54(1), 1-22.

    Landrigan, R.J., Gehlbach, S.H., Rosenblum, B.E, Shoults, J.M., Candelaria, R.M., Barthel, WE, Liddle, J.A., Smrek, A.L., Staehling, N.W., & Sanders, J.E (1975). Epidemic lead absorption near an ore smelter. The role of paniculate lead. New England Journal of Medicine, 292(3), 123-129.

    Marrie, R.A., Wolfson, C., Sturkenboom, M.C., Gout, O., Heinzlef, O., Roullet, E., & Abenhaim, L. (2000). Multiple sclerosis and antecedent infections. Neurology, 54, 2307-2310.

    Minden, S.L., Marder, W.D., Harrold, L.N., & Dor, A. (1993). Multiple sclerosis: A statistical portrait. New York: National Multiple Sclerosis Society.

    Morse, D.L., Landrigan, P.J., Rosenblum, B.F., Hubert, J.S., & Housworth, J. (1979). El Paso revisited: Epidemiologic follow-up of an environmental lead problem. Journal of the American Medical Association, 242, 739-741.

    Noonan, C.W., Kathman, S.J., & White, M.C. (2002). Prevalence estimates for MS in the United States and evidence of an increasing trend for women. Neurology, 58(1), 136-138.

    Poser, C.M., Paty, D.W., Scheinberg, L., McDonald, W.I., Davis, F.A., Ebers, G.C., Johnson, K.P., Sibley, W.A., Silberberg, D.H., & Tourtellotte, WW. (1983). New diagnostic criteria for multiple sclerosis: Guidelines for research protocols. Annals of Neurology, 13(3), 227-231.

    Poser, C.M. (1994). The epidemiology of multiple sclerosis: A general overview. Annals of Neurology, 36(S2), S180-S193.

    Rosenblum, B.F., Shoults, J.M., & Candelaria, R.M. (1976). Lead health hazards from smelter emissions. Texas Medicine, 72(1), 44- 56.

    Sadovnick, A.D., Dyment, D., & Ebers, G.C. (1997). Genetic epidemiology of multiple sclerosis. Epidemiologic Reviews, 19(1), 99- 106.

    Schiffer, R.B., Weitkamp, L.R., Ford, C., & Hall, W.J. (1994). A genetic marker and family history study of the upstate New York multiple sclerosis cluster. Neurology, 44, 329-333.

    Sorensen, T.L., & Ransohoff, R.M. (1988). Etiology and pathogenesis of multiple sclerosis. Seminars in Neurology, 18(3), 287-294.

    Stein, E.G., Schiffer, R.B., Hall, W.J., & Young, N. (1987) Multiple sclerosis and the workplace: Report of an industry-based cluster. Neurology, 37, 1672-1677.

    Weinshenker, E.G. (1996). Epidemiology of multiple sclerosis. Neurological Clinics, 14(2), 291-308.

    Williamson, D.M., & Henry, J.R (2004). Challenges in addressing community concerns regarding clusters of multiple sclerosis and potential environmental exposures. Neuroepidemiology, 23(5), 211- 216.

    Wynn, D.R., Rodriguez, M., O'Fallen, M., & Kurland, L.T. (1990). A reappraisal of the epidemiology of multiple sclerosis in Olmsted County, Minnesota. Neurology, 40, 780-786.

    Judy P. Henry, Ph.D., Dhelia M. Williamson, Ph.D., Randolph Schiffer, M.D., Laurie Wagner, Jeffrey Shire, M.S., Matthew Garabedian, M.D., M.P.H.

    Copyright National Environmental Health Association Jun 2007

    Source Journal of Environmental Health. Provided by ProQuest Information and Learning. All rights Reserved. (13/06/07)

    New research into multiple sclerosis
    Multiple Sclerosis (MS) is a condition of the central nervous system which affects over 16,000 Australians. Today Alex is joined by regular 666 dietitian Caroline Salisbury, with Robbie Costmeyer, chief executive officer of MS Australia, and Professor Anne-Louise Ponsonby a researcher with the Ausimmune study.

    "Sclerosis" refers to damage and inflammation of the protective sheet of fatty tissue or myelin which surrounds the nerve fibres of the central nervous system. MS involves temporary or permanent interruption to these nervous signals. Symptoms can include loss of co-ordination, fatigue, numbness and changes in vision. MS is more likely to be diagnosed in young adults between 20 and 40 years old, and it's twice as likely to affect women as men.

    New Australian research is providing important information about environmental factors and the development of MS. It has been known for some time that there is a strong latitude related gradient in the occurrence of several auto immune diseases including MS. The Ausimmune study is tracking the occurrence of the first demyelinating episode or FDE, an inflammatory condition in which the myelin is disrupted. Professor Ponsonby and the Ausimmune team of researchers have released some preliminary results which confirm that MS becomes more common as you move further north or south from the equator. Even within Australia the occurrence of MS varies with around 11.9 cases per 100,000 people and 75 per 100,000 in Tasmania. The question is which environmental factors play a part ?, including the role of sunlight and Vitamin D in the development and progression of MS.

    MS can impact on numerous aspects of life and one of these is diet. There is yet to be any direct evidence of the role of diet in the development of MS, including risk of MS in countries with high intakes of saturated fats, and lower intakes of polyunsaturated fats. Essential fatty acids including omega 6 and omega 3 are significant in the structure of the brain tissue and myelin sheath, with 1/3 of the myelin sheath is polyunsaturated. Like most chronic conditions, diet and nutritional supplements can be seen as a possible treatment, but the research is unfortunately inconclusive.

    One major study on the role of diet in the progression of MS was undertaken by Dr Roy Swank who treated MS patients over a period of 34 years. These patients followed a diet including less than 20g of saturated fats per day, as well as a high intake of polyunsaturated fats. Swank reported lower death rates and lower progression for patients following the "swank diet". An Australian version of this diet has been developed by Dr George Jelinek.

    Caroline comments that unfortunately it can be difficult to confirm Swank's research with large population based diet trials. She suggests that a Mediterranean type diet with high levels of antioxidants including monounsaturated and polyunsaturated fats, high fish consumption along with plant based omega 3s including walnuts and linseeds. She also suggests that high levels of vitamin and mineral supplements should be used with caution. They can be expensive, as well as unnecessary for many and can have unforseen impacts on the absorption of other nutrients and can interact with medications. Individuals with MS need to be cautious of restrictive diets which include entire food groups such as gluten or milk free diets. It's always best to check with a dietitian who has experience with diet and MS.

    MS can also have nutritional consequences which can impact on the nutrition status of people with MS. Depending on the level of symptoms, energy intake may be affected leading to changes in weight, and one study found poor intake of a range of nutrients including zinc, iron, folate and vitamin D. MS can affect diet in numerous ways by impacting on people's ability to shop and prepare food. Fatigue can also mean a lower intake at meals, with a need for high energy snacks and drinks. MS can affect gut motility so people may suffer early satiety or fullness after a meal, and side effects such as reflux are common as is constipation due to reduced mobility and reduced volume of food.

    Medication which are commonly used in MS may have side effects such as nausea, dry mouth and diarrhoea. Caroline suggests that it is important that people with MS or their carers should discuss side effects with pharmacist or GP.

    Source: ABC 666 Canberra  © 2007 ABC (04/06/07)

    Veterans' ills may show MS link to Gulf War
    Possible connection is subject of studies, legislation.

    Bob Wolz blamed dehydration and the blazing sun for his mysterious blackouts during the first Gulf War.

    But he had no idea what to think when his left arm and leg got weaker and thinner than his right limbs. The problems continued after he returned home, and last year, two years after retiring from the military, doctors diagnosed Wolz with multiple sclerosis -- which the Army veteran now considers a lingering wound from his first tour of duty.

    "I was exposed to something," he said.

    Wolz, of Rineyville, Ky., is among a growing number of Gulf War veterans who have developed the chronic neurological disease, suggesting a possible connection to toxic substances or other environmental triggers during wartime.

    That possible link, hinted at in a couple of past studies, is the subject of new research, funding efforts and legislation. A Georgetown University doctor who identified more than 5,000 service-connected MS cases is now looking specifically at veterans of the Gulf War in 1991.

    The National Multiple Sclerosis Society is pushing for $15 million in research funding for the Department of Defense. And a bill before Congress would help veterans with MS get disability benefits more easily.

    Backing up such efforts is a study published in 2005 showing that MS among Kuwaitis more than doubled between 1993 and 2000.

    So far, there are no firm statistics on the number of Gulf War veterans with MS. But Julie Mock of Washington state, president of an advocacy group called Veterans of Modern Warfare, said she knows of at least 600 nationwide and gets calls and e-mails from new sufferers every day.

    "People are coming out of the woodwork," said Mock, a 40-year-old Gulf War veteran with MS.

    Wolz, 42, is not surprised that other soldiers who served in the Gulf struggle with the illness. Looking back, he recalls several possible triggers, from anthrax vaccinations to chemical exposure. He was a decontamination specialist with a chemical unit, and was in Kuwait when the Iraqi oil wells burned, turning the sky so black he couldn't tell whether it was night or day.

    Experts said studying veterans like Wolz could have wide implications for the 400,000 Americans with MS, which has no known cause. Dr. John Richert of the MS society echoed others, saying that finding an environmental trigger "would break new ground," pointing the way toward better treatments or even a cure.

    MS takes its toll

    On a recent morning, Wolz sat at the edge of the examining table at the Louisville Veterans Affairs Medical Center as Dr. Manjari Motaparthi checked the strength and feeling on both sides of his body.

    She asked him to follow her finger with his eyes, lightly touched his cheeks, then pressed on his left leg and noted, "It's a little bit weak here."

    "It hasn't gotten better," he told her. "It hasn't gotten worse, either … well, maybe a little bit."

    Over the years, MS has taken its toll. In addition to losing muscle tissue, Wolz can't stand the heat, is prone to falls and has memory problems that he copes with by writing notes to himself.

    Wolz said he hasn't had trouble getting military benefits for his disability, as some vets have. But getting diagnosed wasn't easy, he said. None of the doctors he visited at military bases and in war zones found any serious problems.

    Then, after Wolz retired from the Army in 2004, his family doctor in Elizabethtown told him he might have suffered a small stroke. He was referred to a physical therapist at the VA, who disagreed and suggested more tests.

    A scan confirmed MS, which occurs when a fatty tissue that helps nerve fibers conduct electrical impulses -- called myelin -- is lost. Wolz had the most common type, relapsing-remitting, which is characterized by flare-ups and recoveries.

    The main treatment, giving himself shots of interferon beta-1 three times a week, has proved difficult. "It took 45 minutes before I could even do it the first time," said Wolz, who is now working as a military analyst. "I do not like needles."

    Dr. Stephen Kirzinger, medical director of the University of Louisville's MS Care Center program, said he is intrigued by the research exploring the connection between MS and the Gulf War, since he has treated several veterans at his local clinics.

    MS is thought to be an autoimmune disease related at least partly to genetics, and is more common among women and people who spent their mid-teenage years in northern climates. While researchers have long suspected a trigger, they have mostly considered infectious agents such as viruses.

    But the Georgetown study, led by Dr. Mitchell T. Wallin and published in the Annals of Neurology in 2003, said the higher-than-normal MS rates found among veterans who served from 1960 to 1994 "strongly imply a primary environmental factor in the cause or precipitation of this disease."

    Other studies, which looked more generally at the collection of problems dubbed "Gulf War Syndrome," mention the possible dangers of oil-well smoke, vaccines and sarin from the destruction of weapons. Army Times reported last month that researchers at Boston University have all but determined exposure to sarin gas in 1991 is the cause of Gulf War Syndrome.

    Mock said she thinks scientists will find a link because the anecdotal evidence is undeniable. Among a detachment of 60 people who served with her in southern Iraq, she said, "there were three of us within 100 feet of each other" who now have MS.

    Benefits and research

    As research continues, so do efforts to help these veterans.

    U.S. Sen. Patty Murray, D-Wash., reintroduced a bill in March to help them qualify for VA disability benefits. The legislation would remove a seven-year limit veterans now face for connecting their MS to military service after an honorable discharge. The bill would also ensure the condition is presumed to be caused by military service if diagnosed later.

    Congress is also expected to decide by August about giving the Defense Department the $15 million in federal research funding. Shawn O'Neail, associate vice president of federal government relations for the MS society, said the money would go to the department's Congressionally Directed Medical Research Programs, which would distribute it using a peer-reviewed application process "with a preference given to combat service" studies.

    "It's definitely something that needs to be researched further," O'Neail said. "Whatever the benefits of the research are, they could be applied to everyone with MS."

    Meanwhile, Wolz continues his personal battle. Motaparthi called his prognosis "favorable" and said he may be able to keep the disease at current levels if the injections continue working.

    Nothing is assured, however; half the people with his type of MS go on to develop another type in which the disease steadily gets worse.

    Wolz's wife, Linda, said although her husband is dealing well with the disease, it has changed family dynamics. Their children are gentler toward her husband, she said, more like parents.

    "I get worried when he's here alone," said daughter Bianca, 16. "I don't want him to fall."

    Wolz tries not to dwell on the possibility that he may someday need a wheelchair to get around safely, or that MS will compromise his future.

    "If I focus on that, I can't focus on fighting it," he said. "I have too many things I want to do in life."

    Source: VA Watchdog.com (04/06/07)

    New Research To Examine Increased Risk of Multiple Sclerosis Among US Veterans
    Cases Suggest MS Could be Driven by Environmental Factors.

    Emerging research has identified a possible increased risk of developing multiple sclerosis (MS) among Gulf War veterans. Data from the Department of Veterans Affairs MS Centres of Excellence and the Department of the Defense will help further investigate the link.

    Of veterans with MS who were deployed in the Gulf War, more than 500 have been determined to be a service-connected by the VA. There are likely many unidentified cases. The results of this new study could show progress into the causes of MS, while unveiling another health risk for American veterans, in an environment of increasing concern about post-service care.

    “These preliminary data suggest a potential link between military service in the Gulf War and an increased risk of developing MS. We could be one step closer to unlocking the environmental triggers of MS,” Mitch Wallin, MD, MPH, lead investigator on the study, said. “These results are important to the health care of our military veterans and all individuals living with MS. There is a critical need for further research.”

    Dr. Wallin is Associate Professor of Neurology at Georgetown University School of Medicine and Associate Director of Clinical Care at the VA MS Center of Excellence-East in Baltimore.

    Recent empirical evidence also shows an increase of MS right after the Gulf War among Kuwaitis. These data suggest that the cases of MS are, at least in part, being driven by environmental factors. Gulf War veterans who served in the combat theatre were exposed to a number of environmental agents including multiple vaccinations, viral and parasitic organisms, smoke from oil well fires, and more. Despite several decades of research, MS and its causes still are not fully understood, and there is no cure.

    Overall federal funding for MS research has declined in recent years. However, Congress currently is looking at a possible $15 million appropriation into Department of Defense research that could help further explore the causes of MS.

    Source: I am a MS Activist Blog

    Related Items
    Bacteria
    Biomarkers And MicroRNA
    Blood Tests And MS
    Botox
    Brain Inflammation
    Brain Iron Deposits
    Cancer And MS
    Chronic Cerebrospinal Venous Insufficiency (CCSVI)
    Cognition and Cognitive Issues
    CRMP-2
    Diet And MS
    Drugs
    Endo-parasites & 'Helpful' Organisms
    Ethnic Groups and MS
    Exercise And MS
    Genetics and MS
    Hormones And MS
    Immune Cells And MS
    Kallikrein 6
    Lightning Process® And Multiple Sclerosis
    Lipids And MS
    Lymphoid Tissue Inducer (LTi) Cells
    Medical Imaging
    MS Stem Cell Research & Treatment
    MS Symptoms
    Myelin
    Nerve And Brain Cells
    Neuropsychiatric and Psychological
    Neurosteroids
    Osteoporosis And MS
    Paediatric MS
    Pain
    Potential Viral Causes Of MS
    Pregnancy And MS
    Quality Of Life
    Stress And MS
    Technology And MS
    The Blood Brain Barrier
    Types Of MS
    Vaccinations & MS
    Vitamin D


    Did you find this information useful? Would you like to comment on this page? Let us know what you think! We welcome all comments and feedback on any aspect of our website - please click here to contact us.