Epidemiology of multiple sclerosis in US veterans: III. Migration and the risk of MS

World War II or Korean Conflict veterans with MS (5,305 in number) and pre-illness-matched controls were compared for residence at birth and entry on active duty (EAD) within three north-south tiers of states in the United States. A strong north-south gradient of MS risk was present. Migrants were defined as those whose birth and EAD tier differed. For white men of World War II, all white men, and all whites, there were highly significant reductions in risk for moves southward from either the north or middle tier, and increases in risk for moves northward from the middle tier. Increases similar in magnitude of middle to north did not attain statistical significance in the few southern-born migrants. For the small groups of black men and white men of Korean service, trends were similar but did not attain significance, whereas for white women, they were of borderline significance. Findings imply an environmental cause for MS, with acquisition years before symptom-onset.     

Epidemiology of multiple sclerosis in U.S. veterans: V. Ancestry and the risk of multiple sclerosis

Self-reported ancestry data for the U.S. population from the 1980 decennial census and multiple sclerosis (MS) risk data derived from a large series of World War II white male veterans with MS and matched controls were aggregated on a state level and analyzed to determine the relationship between ancestry and MS risk. A significant portion of the state-by-state variation in MS risk is explainable statistically by differences in ancestry among state populations, even when geographic latitude is included in analyses. In the main, Swedish and other Scandinavian ancesty is most consistently associated with places with increased MS risk. In some analyses, Italian, French, and (to a lesser extent) Scottish ancestries are also associated with increased risk, whereas English and Dutch ancestries are each associated with decreased risk, but most of these non-Scandinavian correlations may effect predomininatly geography per se. These findings provide evidence that ancestry of the resident population, a confounded measure of genetic susceptibility and cultural evironment, is part of the complicated picture of MS as a disease of place.     

Migration of multiple sclerosis lymphocytes through brain endothelium

CONTEXT: T-lymphocyte migration through the blood-brain barrier is a central event in the process of lesion formation in multiple sclerosis (MS). OBJECTIVES: To assess the ability of lymphocytes derived from the peripheral blood of patients with clinically active and inactive MS to migrate across an artificial model of the blood-brain barrier and to elucidate the molecular mechanisms involved in such a process. DESIGN: We developed an in vitro model of lymphocyte migration using a Boyden chamber coated with a monolayer of human brain microvascular endothelial cells. RESULTS: The rates of migration of lymphocytes obtained from patients with acutely relapsing and active secondary progressive MS was significantly increased compared with those obtained from healthy controls and patients with inactive secondary progressive disease. Ribonuclease protection assays and enzyme-linked immunosorbent assays indicated that monocyte chemoattractant protein 1 and interleukin 8 were the major chemokines produced by brain endothelial cells grown under the culture conditions used for the migration assays. The rate of migration of the MS lymphocytes could be inhibited by 60% with an antimonocyte chemoattractant protein 1 monoclonal antibody, indicating a functional role for this chemokine in the migration process. In agreement with previous reports, we found that the tissue inhibitor of metalloproteinase 1, a matrix metalloproteinase inhibitor, also reduced migration of MS lymphocytes by 50%. CONCLUSIONS: The results demonstrate an increased migration rate of MS T lymphocytes across the brain endothelium barrier and that such migration is dependent on chemokine monocyte chemoattractant protein 1 and on matrix metalloproteinases.     

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.     

Household pets among veterans with multiple sclerosis and age-matched controls. Pilot survey

A pilot study was carried out among 22 Vietnam-era male US veterans with multiple sclerosis (MS) and 55 age- and sex-matched controls for prior exposure to dogs, cats, and animals with a distemperlike illness. No difference in dog ownership, or sick animals, and subsequent human illness was found in the group with MS or the control group. However, the distribution of dogs by indoor-outdoor status, as reported by patients with MS or controls, showed significant variation by tier of residence. Indoor dogs were more common in northern than southern latitudes, and this may be an important finding in light of the variation in the risk of MS with latitude.     

Epidemiology of multiple sclerosis in US veterans. 4. Age at onset.

Age at onset of multiple sclerosis (MS) symptoms was ascertained for subsets of some 4,400 veterans of World War II who had been adjudged 'service-connected' for this condition. Average age at onset was 27.0 years for white men, 27.7 for white women, and 27.5 for black men. The unexpectedly older age for women is attributed to their older age at entry into service. When the coterminous United States was divided into three horizontal tiers of states, we found a strong effect of geography on age at onset. By state of residence at entry into active duty (EAD), white men had an average age at onset of 26.4 years in the northern tier, 27.3 years in the middle, and 28.8 years in the south. Trends were similar for white women and black men. Migrants, defined as those whose birth and EAD tiers differed, showed increasing ages at onset with southward moves. A statistical model used to discriminate between the influence of birth and EAD tiers on age at onset confirmed the significant effect of EAD alone. These data are compatible with the theses that the cause of MS is less common (or less efficient) in locations where the clinical disease is less common, and that its acquisition therefore occurs at an older age in those locales.     

Multiple sclerosis in US veterans of the Vietnam era and later military service: race, sex, and geography

We identified 5345 cases of multiple sclerosis (MS) among US veterans who first entered military service between 1960 and 1994, and who were "service-connected" for MS by the Department of Veterans Affairs (VA). Two controls per case were matched on age, date of service entry, and branch of service. Available for service and VA files were demographic and military data for 4951 cases and 9378 controls. Versus white men, relative risk of MS was significantly higher for all women, at 2.99 for whites, 2.86 for blacks, and 3.51 for those of other races. This was a significant increase from our prior series of veterans of World War II and the Korean Conflict, where white women had a relative risk of 1.79. Risk for black men was higher now (0.67 vs 0.44), while other men remained low (0.30 vs 0.22). Residence at service entry in the northern tier of states had a relative risk of 2.02 versus the southern tier, which was significantly less than the 2.64 for the earlier series. Residence by individual state at birth and service entry for white men further supported this decreasing geographic differential. Such marked changes in geography, sex, and race in such a short interval strongly imply a primary environmental factor in the cause or precipitation of this disease.     

Migration of T-cell subsets in multiple sclerosis and the effect of interferon-beta1a

OBJECTIVES: Migration of inflammatory cells across the blood-brain barrier is a central event in the formation of multiple sclerosis (MS) lesions and is known to be enhanced in MS patients. This study investigates the migration of CD4+ and CD8+ T-cell subsets and the effects of interferon-beta1a (IFN-beta1a) treatment on migration and matrix metalloproteinase-9 (MMP-9) production of these T-cell subsets. MATERIALS AND METHODS: An ex vivo transwell system was established to compare the migratory behaviour of lymphocytes isolated from normal controls and untreated MS patients. In addition, MS patients were investigated longitudinally after initiation of IFN-beta1a treatment. RESULTS: Migration of CD4+ T cells (P < 0.05), but not of CD8+ T cells, was enhanced in untreated MS patients compared with controls and was normalized by treatment with IFN-beta1a. In addition, IFN-beta1a treatment reduced MMP-9 production of CD4+ but not CD8+ T cells. CONCLUSION: Our results indicate that CD4+ T cells, but not CD8+ T cells, contribute to the enhanced ex vivo migration observed in MS.     

Crime among homeless military veterans who abuse substances

This was a study of crime among 188 homeless persons who were in a Veterans' Affairs Medical Center program for substance abusers. The purpose of the study was to find out: (a) what proportion committed crimes, and (b) what other problems, relational factors, and personal attributes predict crime. Data indicate 27% of these homeless veterans committed nuisance offenses, and 41% have committed crimes in the past year. Logistic regression procedures indicated that alcohol and other drug abuse, less education, lack of employment, psychiatric problems, and living with a substance abuser increased the odds of committing crimes. This study also finds that physical and sexual abuse before 18 years of age increases the odds of committing crimes, whereas self-efficacy, ego integrity, and resilience decrease these odds. These latter factors have received scant attention in the literature on homeless substance abusers, and yet they are among the strongest predictors of crime. Implications for psychiatric rehabilitation are discussed.     

Migration and age at onset of multiple sclerosis: some pitfalls of migrant studies

The aim of this study was to compare age at onset of multiple sclerosis (MS) in North African-born and French-born patients. The migrant group consisted of 246 patients who arrived in France during the period 1960-1965. Among these migrants, 27 (11%) had first symptoms before migration. The French-born group consisted of MS patients of same sex and age at the time of the study as migrants who were randomly selected from a large national sample. After controlling for various biases which could explain differences between migrants and French-born patients, we found no differences in mean age at MS onset between the two groups. Therefore, it is likely that MS was acquired by the same age in migrants as in French-born patients. This finding may constitute an indirect support for the hypothesis that the unknown causative factors of MS are equally frequent whatever the latitude of origin.     

Treatment patterns of multiple sclerosis patients: a comparison of veterans and non-veterans using the NARCOMS registry

Multiple sclerosis (MS) is a chronic illness of the central nervous system, with a highly variable clinical course. Available therapies are only partially effective and as a consequence treatment patterns between patients can be varied. Longitudinal databases consisting of large cohorts where successive and sequential data is collected may reveal disease and treatment characteristics not apparent when data is gathered during clinical trials that consist usually of relatively homogeneous patients followed for short durations. We analysed data from the North American Research Committee on Multiple Sclerosis registry, a self-reported database, to assess MS patient characteristics and treatment patterns, with a focus on veterans. We show that the Veteran Healthcare Administration (VHA) system of medical centres care for a greater number of patients with higher average disability but not necessarily patients who report primary progressive or actively worsening disease. We also show that the VHA medical centres appear to better provide multidisciplinary care, particularly in the areas of social work, physical therapy and urology. In general, treatment patterns for symptomatic therapies follow similar patterns across veterans and non-veterans groups. Treatment patterns for immunomodulatory agents suggest that VHA veterans use IMA less frequently than either non-VHA veterans or non-veterans.     

Non-fatal self-harm in Scottish military veterans: a retrospective cohort study of 57,000 veterans and 173,000 matched non-veterans

Social Psychiatry and Psychiatric Epidemiology - Although suicide risk in veterans has been widely studied, there is little information on the risk of non-fatal self-harm in this population. We...