Environmental modifiable risk factors for multiple sclerosis: Report from the 2016 ECTRIMS focused workshop

Multiple sclerosis (MS) is an inflammatory and neurodegenerative demyelinating disease of the central nervous system (CNS), most likely autoimmune in origin, usually beginning in early adulthood. The aetiology of the disease is not well understood; it is viewed currently as a multifactorial disease which results from complex interactions between genetic predisposition and environmental factors, of which a few are potentially modifiable. Improving our understanding of these factors can lead to new and more effective approaches to patient counselling and, possibly, prevention and management of the disease. The 2016 focused workshop of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) addressed the topic of environmental, modifiable risk factors for MS, gathering experts from around the world, to collate experimental and clinical research into environmental factors that have been associated with the disease onset and, in a few cases, disease activity and progression. A number of factors, including infections, vitamin D deficiency, diet and lifestyle factors, stress and comorbidities, were discussed. The meeting provided a forum to analyse available evidence, to identify inconsistencies and gaps in current knowledge and to suggest avenues for future research.

[1]  H. Tremlett,et al.  Factors associated with onset, relapses or progression in multiple sclerosis: A systematic review , 2017, Neurotoxicology.

[2]  D. Younger,et al.  Epidemiology of Multiple Sclerosis. , 2016, Neurologic clinics.

[3]  Ba,et al.  Mendelian randomization shows a causal effect of low vitamin D on multiple sclerosis risk , 2016, Neurology: Genetics.

[4]  Altmann,et al.  Phase 2 baseline versus treatment clinical trial of the HIV drug raltegravir in patients with active relapsing remitting multiple sclerosis: the INSPIRE study results , 2016 .

[5]  Laura M Cox,et al.  Alterations of the human gut microbiome in multiple sclerosis , 2016, Nature Communications.

[6]  Krishna R. Kalari,et al.  Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls , 2016, Scientific Reports.

[7]  H. Butzkueven,et al.  Observational data: Understanding the real MS world , 2016, Multiple sclerosis.

[8]  A. Ascherio,et al.  Vitamin D Status During Pregnancy and Risk of Multiple Sclerosis in Offspring of Women in the Finnish Maternity Cohort. , 2016, JAMA neurology.

[9]  E. Waubant,et al.  Gut microbiota composition and relapse risk in pediatric MS: A pilot study , 2016, Journal of the Neurological Sciences.

[10]  C. Wolfson,et al.  Health-related quality of life in multiple sclerosis , 2016, Neurology.

[11]  R. Marrie,et al.  Examining the effects of comorbidities on disease-modifying therapy use in multiple sclerosis , 2016, Neurology.

[12]  A. Ascherio,et al.  Epidemiology of Multiple Sclerosis: From Risk Factors to Prevention—An Update , 2016, Seminars in Neurology.

[13]  T. Dwyer,et al.  Population attributable fractions and joint effects of key risk factors for multiple sclerosis , 2016, Multiple sclerosis.

[14]  E. Mowry,et al.  High consumption of coffee is associated with decreased multiple sclerosis risk; results from two independent studies , 2016, Journal of Neurology, Neurosurgery & Psychiatry.

[15]  H. Wiendl,et al.  Implications of dietary salt intake for multiple sclerosis pathogenesis , 2016, Multiple sclerosis.

[16]  T. Dwyer,et al.  Frequency of Comorbidities and Their Association with Clinical Disability and Relapse in Multiple Sclerosis , 2016, Neuroepidemiology.

[17]  B. Hemmer,et al.  B cell-directed therapies in multiple sclerosis. , 2016, Neurodegenerative disease management.

[18]  D. Goodin,et al.  Association of Vitamin D Levels With Multiple Sclerosis Activity and Progression in Patients Receiving Interferon Beta-1b. , 2015, JAMA neurology.

[19]  T. Holmøy,et al.  Body mass index influence interferon-beta treatment response in multiple sclerosis , 2015, Journal of Neuroimmunology.

[20]  M. Bottai,et al.  Effect of Smoking Cessation on Multiple Sclerosis Prognosis. , 2015, JAMA neurology.

[21]  C. Greenwood,et al.  Vitamin D and Risk of Multiple Sclerosis: A Mendelian Randomization Study , 2015, PLoS medicine.

[22]  J. Hillert,et al.  The Swedish MS registry – clinical support tool and scientific resource , 2015, Acta neurologica Scandinavica.

[23]  C. Wolfson,et al.  Is high socioeconomic status a risk factor for multiple sclerosis? A systematic review , 2015, European journal of neurology.

[24]  D. Hafler,et al.  Multiple sclerosis—a quiet revolution , 2015, Nature Reviews Neurology.

[25]  B. Hemmer,et al.  Role of the innate and adaptive immune responses in the course of multiple sclerosis , 2015, The Lancet Neurology.

[26]  E. Granieri,et al.  Body size and the risk of multiple sclerosis in Norway and Italy: The EnvIMS study , 2015, Multiple sclerosis.

[27]  M. Ramanathan,et al.  Cardiovascular risk factors are associated with increased lesion burden and brain atrophy in multiple sclerosis , 2015, Journal of Neurology, Neurosurgery & Psychiatry.

[28]  H. Siebner,et al.  Trichuris suis ova therapy in relapsing multiple sclerosis is safe but without signals of beneficial effect , 2015, Multiple sclerosis.

[29]  M. Niino,et al.  Genetic polymorphisms related to vitamin D and the therapeutic potential of vitamin D in multiple sclerosis. , 2015, Canadian journal of physiology and pharmacology.

[30]  R. Khanna,et al.  The Development of Prophylactic and Therapeutic EBV Vaccines. , 2015, Current topics in microbiology and immunology.

[31]  R. Zheng,et al.  Chronic caffeine treatment protects against experimental autoimmune encephalomyelitis in mice: Therapeutic window and receptor subtype mechanism , 2014, Neuropharmacology.

[32]  P. Bhargava,et al.  The vitamin D to ameliorate multiple sclerosis (VIDAMS) trial: study design for a multicenter, randomized, double-blind controlled trial of vitamin D in multiple sclerosis. , 2014, Contemporary clinical trials.

[33]  T. Olsson,et al.  Obesity during childhood and adolescence increases susceptibility to multiple sclerosis after accounting for established genetic and environmental risk factors. , 2014, Obesity research & clinical practice.

[34]  B. V. Pedersen,et al.  Stressful life-events in childhood and risk of multiple sclerosis: a Danish nationwide cohort study , 2014, Multiple sclerosis.

[35]  T. Olsson,et al.  Interaction between adolescent obesity and HLA risk genes in the etiology of multiple sclerosis , 2014, Neurology.

[36]  N. Nielsen,et al.  Major stressful life events in adulthood and risk of multiple sclerosis , 2014, Journal of Neurology, Neurosurgery & Psychiatry.

[37]  T. Olsson,et al.  Alcohol as a modifiable lifestyle factor affecting multiple sclerosis risk. , 2014, JAMA neurology.

[38]  Ludwig Kappos,et al.  Vitamin D as an early predictor of multiple sclerosis activity and progression. , 2014, JAMA neurology.

[39]  C. Pozzilli,et al.  Effects of Bacille Calmette-Guérin after the first demyelinating event in the CNS , 2014, Neurology.

[40]  T. Olsson,et al.  Smoking and multiple sclerosis susceptibility , 2013, European Journal of Epidemiology.

[41]  J. Pakpoor,et al.  Childhood obesity and risk of pediatric multiple sclerosis and clinically isolated syndrome , 2013, Neurology.

[42]  M. Pirinen,et al.  Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis , 2013, Nature Genetics.

[43]  G. Hallmans,et al.  Smoking as a risk factor for multiple sclerosis , 2013, Multiple sclerosis.

[44]  C. Tench,et al.  Tobacco smoking and disability progression in multiple sclerosis: United Kingdom cohort study , 2013, Brain : a journal of neurology.

[45]  K. Dear,et al.  The physical anthropometry, lifestyle habits and blood pressure of people presenting with a first clinical demyelinating event compared to controls: The Ausimmune study , 2013, Multiple sclerosis.

[46]  T. Sørensen,et al.  Childhood body mass index and multiple sclerosis risk: a long-term cohort study , 2013, Multiple sclerosis.

[47]  A. Ascherio,et al.  Caffeine and alcohol intakes have no association with risk of multiple sclerosis , 2013, Multiple sclerosis.

[48]  C. A. Speck-Hernandez,et al.  Organic Solvents as Risk Factor for Autoimmune Diseases: A Systematic Review and Meta-Analysis , 2012, PloS one.

[49]  J. Lünemann,et al.  The initiation and prevention of multiple sclerosis , 2012, Nature Reviews Neurology.

[50]  R. Spang,et al.  T cells become licensed in the lung to enter the central nervous system , 2012, Nature.

[51]  M. Filippi,et al.  A randomised, double blind, placebo controlled trial with vitamin D3 as an add on treatment to interferon β-1b in patients with multiple sclerosis , 2012, Journal of Neurology, Neurosurgery & Psychiatry.

[52]  S. Mellgren,et al.  Effect of vitamin D3 supplementation on relapses, disease progression, and measures of function in persons with multiple sclerosis: exploratory outcomes from a double-blind randomised controlled trial , 2012, Multiple sclerosis.

[53]  T. Olsson,et al.  High body mass index before age 20 is associated with increased risk for multiple sclerosis in both men and women , 2012, Multiple sclerosis.

[54]  F. Paul,et al.  Efficacy of Vitamin D Supplementation in Multiple Sclerosis (EVIDIMS Trial): study protocol for a randomized controlled trial , 2012, Trials.

[55]  F. Barkhof,et al.  Efficacy of vitamin D3 as add-on therapy in patients with relapsing–remitting multiple sclerosis receiving subcutaneous interferon beta-1a: A Phase II, multicenter, double-blind, randomized, placebo-controlled trial , 2011, Journal of the Neurological Sciences.

[56]  D. Dreyfus Autoimmune disease: A role for new anti-viral therapies? , 2011, Autoimmunity reviews.

[57]  K. Berer,et al.  Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination , 2011, Nature.

[58]  M. Stein,et al.  A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis , 2011, Neurology.

[59]  K. Myhr,et al.  Dietary Vitamin D3 Supplements Reduce Demyelination in the Cuprizone Model , 2011, PloS one.

[60]  J. Correale,et al.  The impact of environmental infections (parasites) on MS activity , 2011, Multiple sclerosis.

[61]  Simon C. Potter,et al.  Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis , 2011, Nature.

[62]  A. Ascherio,et al.  Smoking and increased risk of multiple sclerosis: parallel trends in the sex ratio reinforce the evidence. , 2011, Annals of Epidemiology.

[63]  A. Bar-Or,et al.  Cholecalciferol plus calcium suppresses abnormal PBMC reactivity in patients with multiple sclerosis. , 2011, The Journal of clinical endocrinology and metabolism.

[64]  G. Giovannoni,et al.  Smoking and Multiple Sclerosis: An Updated Meta-Analysis , 2011, PloS one.

[65]  P. Kokhaei,et al.  Therapeutic Effect of Vitamin D3 in Multiple Sclerosis Patients , 2011, Immunological investigations.

[66]  J. Damoiseaux,et al.  Vitamin D as a T-cell modulator in multiple sclerosis. , 2011, Vitamins and hormones.

[67]  S. Mazmanian,et al.  Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis , 2010, Proceedings of the National Academy of Sciences.

[68]  G. Giovannoni,et al.  Multiple sclerosis: risk factors, prodromes, and potential causal pathways , 2010, The Lancet Neurology.

[69]  J. M. Burton,et al.  A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis , 2010, Neurology.

[70]  A. Ascherio,et al.  Primary infection with the Epstein‐Barr virus and risk of multiple sclerosis , 2010, Annals of neurology.

[71]  Jing Cui,et al.  Integration of genetic risk factors into a clinical algorithm for multiple sclerosis susceptibility: a weighted genetic risk score , 2009, The Lancet Neurology.

[72]  T. Chitnis,et al.  Body size and risk of MS in two cohorts of US women , 2009, Neurology.

[73]  G. Ebers,et al.  Multiple sclerosis: major histocompatibility complexity and antigen presentation , 2009, Genome Medicine.

[74]  T. Olsson,et al.  Tobacco smoking, but not Swedish snuff use, increases the risk of multiple sclerosis , 2009, Neurology.

[75]  R. Marrie,et al.  Comorbidity delays diagnosis and increases disability at diagnosis in MS , 2009, Neurology.

[76]  Ariel Miller,et al.  Impact of exposure to war stress on exacerbations of multiple sclerosis , 2008, Annals of neurology.

[77]  A. Lutterotti,et al.  Smoking is a risk factor for early conversion to clinically definite multiple sclerosis , 2008, Multiple sclerosis.

[78]  A. Ascherio,et al.  Environmental risk factors for multiple sclerosis. Part I: The role of infection , 2007, Annals of neurology.

[79]  A. Ascherio,et al.  Infectious mononucleosis and risk for multiple sclerosis: A meta‐analysis , 2006, Annals of neurology.

[80]  D. Mohr,et al.  The role of stress-response systems for the pathogenesis and progression of MS. , 2005, Trends in immunology.

[81]  V. De Rosa,et al.  Leptin increase in multiple sclerosis associates with reduced number of CD4(+)CD25+ regulatory T cells. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[82]  D. Gilden Infectious causes of multiple sclerosis , 2005, The Lancet Neurology.

[83]  D. Mohr,et al.  Association between stressful life events and exacerbation in multiple sclerosis: a meta-analysis , 2004, BMJ : British Medical Journal.

[84]  C. Johansen,et al.  The risk of multiple sclerosis in bereaved parents , 2004, Neurology.

[85]  Graham M Lord,et al.  Requirement for Leptin in the Induction and Progression of Autoimmune Encephalomyelitis1 , 2001, The Journal of Immunology.

[86]  C. Martyn,et al.  Migrant studies in multiple sclerosis , 1995, Progress in Neurobiology.

[87]  A. Sadovnick,et al.  Genetics of Multiple Sclerosis , 1995, Neurologic clinics.

[88]  J. Lumley AUSTRALIA , 1920, The Lancet.