Data for this review were identified by searches of MEDLINE (1965–2004) with the search terms “multiple sclerosis” and “case-control”, “cohort”, “ecologic”, “cluster”, “infection”, “measles”, “mumps”, “rubella”, “varicella”, “infectious mononucleosis”, “EBV”, “Chlamydia”, “vaccination”, “hepatitis B”, “organic solvents”, “trauma”, “stress”, “occupation”, “sunlight”, “vitamin D”, “risk factors”, “virus”, “dietary”, “fat”, “nutrition”, “hormones”, and “oral contraceptive pill”.
ReviewEnvironmental risk factors in multiple sclerosis aetiology
Section snippets
Pathophysiology
MS is thought to be a cell-mediated autoimmune disease of the CNS.6 Evidence to support this concept of auto immunity includes (1) predominance of women affected, similar to autoimmune disorders such as rheumatoid arthritis and systemic lupus erythematosus;7 (2) transient amelioration of disease activity during pregnancy, a relatively immunosuppressed state;8 (3) association with other autoimmune diseases both in affected individuals and their family members;9 (4) association with HLA type;10
A complex disease
MS is conceptualised as a complex disease, in which several environmental factors act together in a genetically susceptible individual to cause disease. Family members of affected individuals have a greater risk of disease than the general population.15, 16 Half-siblings of affected persons have roughly half the risk of full siblings of developing MS, and adopted siblings have no greater risk than the general population.16 This indicates that genetic factors do contribute to an individual's
Descriptive epidemiology
The geographic and temporal variations in the incidence and prevalence of MS have been intensively studied. However, it is important to note that several difficulties may arise when comparing incidence and prevalence studies from different areas or time intervals: (1) the populations studied may vary with respect to their size, age distribution, and ethnicity; (2) there may be differences between studies in the completeness of case ascertainment (affected by access to medical care, availability
Analytic epidemiology
Associations between putative environmental risk factors and disease are assessed using observational studies. Ecological studies look for associations at the population or group level. However, they are subject to the ecological fallacy if the association observed between variables at the group level is then applied to individuals.40 In a case-control study, individuals with and without disease are compared with respect to risk factors (exposures) of interest.41 This design is efficient for
Environmental risk factors
Potential risk factors that are commonly studied include infection, vaccinations, stress, occupation, climate, and diet. The roles of diet and sex hormones in the aetiology of MS are discussed elsewhere.45 The reason they are not discussed here is because the data are of insufficient quantity and quality to adequately assess whether diet and sex hormones play a causal role in MS.
Conclusion
Studying the role of environmental risk factors in the aetiology of MS is difficult for several reasons. Any given environmental agent may be only one of many factors capable of causing MS in a genetically susceptible individual, and these factors might be neither necessary or sufficient causes. The interaction of the components of cause may vary from study to study, producing inconsistent results.149 Exposure to putative agents is likely to be highly prevalent among individuals with and
Search strategy and selection criteria
References (148)
- et al.
The epidemiology of autoimmune diseases
Autoimmun Rev
(2003) - et al.
Genetics of multiple sclerosis
Lancet
(2004) - et al.
Evidence for genetic basis of multiple sclerosis
Lancet
(1996) - et al.
The worldwide prevalence of multiple sclerosis
Clin Neurol Neurosurg
(2002) - et al.
Migrant studies in multiple sclerosis
Prog Neurobiol
(1995) - et al.
A study of measles virus and canine distemper virus antibodies, and of childhood infections in multiple sclerosis patients and controls
J Neurol Sci
(1982) - et al.
Problems of experimental trials of therapy in multiple sclerosis
Ann N Y Acad Sci
(1965) - et al.
New diagnostic criteria for multiple sclerosis: guidelines for research protocols
Ann Neurol
(1983) - et al.
Recommended diagnostic criteria for multiple sclerosis: guidelines from the international panel on the diagnosis of multiple sclerosis
Ann Neurol
(2001) - et al.
Application of the new McDonald criteria to patients with clinically isolated syndromes suggestive of multiple sclerosis
Ann Neurol
(2002)
Multiple sclerosis
Continuum
A 21 point unifying hypothesis on the etiology and treatment of multiple sclerosis
Can J Neurol Sci
Rate of pregnancy-related relapse in multiple sclerosis
N Engl J Med
Autoimmune disease in first-degree relatives of patients with multiple sclerosis. A UK survey
Brain
Axonal transection in the lesions of multiple sclerosis
N Engl J Med
Neurodegeneration in multiple sclerosis: relationship to neurological disability
Prog Clin Neurosci
Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination
Ann Neurol
A genetic basis for familial aggregation in multiple sclerosis
Nature
A population-based study of multiple sclerosis in twins: update
Ann Neurol
A reassessment of the distribution of multiple sclerosis. Part one
Acta Neurol Scand
The prevalence of multiple sclerosis in Tayside, Scotland: do latitudinal gradients really exist?
J Neurol
The use of standardized incidence and prevalence rates in epidemiological studies on multiple sclerosis. A meta-analysis study
Neuroepidemiology
Multiple sclerosis in Finland: incidence trends and differences in relapsing remitting and primary progressive disease courses
J Neurol Neurosurg Psychiatry
Latitudinal variation in the prevalence of multiple sclerosis in Ireland, an effect of genetic diversity
J Neurol Neurosurg Psychiatry
Epidemiology of multiple sclerosis in U.S. Veterans: V. Ancestry and the risk of multiple sclerosis
Ann Neurol
Multiple sclerosis in Oslo, Norway: prevalence on 1 January 1995 and incidence over a 25-year period
Eur J Neurol
Multiple sclerosis epidemiology in Sardinia: evidence for a true increasing risk
Acta Neurol Scand
Multiple sclerosis among immigrants in Greater London
BMJ
Latitude, migration, and the prevalence of multiple sclerosis
Am J Epidemiol
Multiple sclerosis among United Kingdom-born children of immigrants from the Indian subcontinent, Africa and the West Indies
J Neurol Neurosurg Psychiatry
Risk of multiple sclerosis related to age at immigration to Israel
Arch Neurol
Multiple sclerosis and age at migration
Am J Epidemiol
The age-range of risk of developing multiple sclerosis. Evidence from a migrant population in Australia
Brain
Cluster studies in multiple sclerosis
Neurology
A multiple sclerosis cluster associated with a small, north-central Illinois community
Arch Environ Health
A neurological disease cluster at a manufacturing plant
Arch Environ Health
Multiple sclerosis in the Faroe Islands: I. clinical and epidemiological features
Ann Neurol
Analysis of the ‘epidemic’ of multiple sclerosis in the Faroe Islands I. Clinical and epidemiological aspects
Neuroepidemiology
Analysis of the ‘epidemic’ of multiple sclerosis in the Faroe Islands II. Biostatistical aspects
Neuroepidemiology
Ecologic studies of multiple sclerosis
Neurology
Case-control studies in multiple sclerosis
Neurology
Historical cohort studies in multiple sclerosis
Neurology
Smoking and health: report of the Advisory Committee to the Surgeon General
The latent period of multiple sclerosis: a critical review
Epidemiology
A systematic review of several potential non-genetic risk factors for multiple sclerosis
Neuroepidemiology
Is Chlamydia pneumoniae present in brain lesions of patients with multiple sclerosis?
J Clin Microbiol
Examination of eight cases of multiple sclerosis and 56 neurological and non-neurological controls for genomic sequences of measles virus, canine distemper virus, simian virus 5 and rubella virus
J Gen Virol
Measles virus nucleotide sequences: detection by hybridization in situ
Science
No measles virus genetic information detected in multiple sclerosis-derived brains
Ann Neurol
Multiple sclerosis and viruses: an overview
Neurology
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