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Objectives and Methods: The interaction between the two best documented risk factors (human leukocyte antigen [HLA] class II [DRB1*1501 positivity] and Epstein-Barr virus [elevated Epstein-Barr nuclear antigen 1 (EBNA-1) antibody reactivity]) for multiple sclerosis (MS) was studied in a case-control study of biobank samples from 109 MS cases and 212 matched referents., Results: Multivariate logistic regression analysis showed that both were statistically significant in both sexes. HLA DRB1*1501-positive referents had higher EBNA-1 reactivity than HLA-negative referents. Less EBNA-1 reactivity was required to increase the MS risk in HLA DRB1*1501-positives than in HLA-negatives., Conclusion: We suggest that HLA DRB1*1501-positive individuals have an increased vulnerability to EBV-induced autoimmunity.

Objective: To estimate the effect of smoking on the risk for progression in multiple sclerosis (MS)., Methods: Self-reported data were used on smoking habits in 122 incident cases with disability assessments made after a median of 6 years disease duration., Results: Ever smokers were more likely to have progressive disease compared with never smokers (P < 0.01). This was most pronounced in ever smokers with early smoking debut (< or = 15 years of age) for whom progressive disease was significantly more likely and occurred at an earlier age, compared with those with later smoking debut (P < 0.01 for both) or never smokers (P < 0.01 for both). Earlys moking start also predisposed to a progressive disease from onset when compared with never smokers (P = 0.012). A multivariate Cox regression analysis of sex, age at disease onset (above vs. under median) and smoking (ever vs. never) status showed that cases with late disease onset had three times higher risk and ever smokers had twice as high a risk for progression., Conclusion: Past smoking is associated with a worsened prognosis in MS. The negative effect from smoking is most obvious in ever smokers with early smoking debut, which also affects MS phenotype significantly.

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.

Objective: To investigate the association between human herpesviruses and multiple sclerosis (MS), as well as between measles virus and MS., Methods: The authors identified prospectively collected serum samples from 73 MS cases and retrospective sera from 161 MS cases in two population-based serum bank registers. Analyses of IgG antibody responses in cases and matched referents were performed for Epstein-Barr virus (EBV [EBNA-1 and VCA]), human herpesvirus 6 (HHV-6), herpes simplex virus (HSV), varicella zoster virus (VZV), and measles., Results: All cases showed signs of past EBV infection. High activity to EBNA-1 and HHV-6 significantly (borderline significance for HHV-6) increased the risk for MS in prospective sera. A discrepancy between activities to EBNA-1 and VCA was striking in MS samples collected less than 5 years before relapsing-remitting MS onset, where high activity to EBNA-1 significantly increased, and high VCA activity significantly decreased the risk for MS. There was no support for major causal roles for HSV, VZV, or measles., Conclusion: Individuals who will develop MS exhibit an altered immune response against the EBV virus characterized by a high IgG activity to EBNA-1 in the absence of high activity to VCA, this being most pronounced in the 5-year period preceding MS onset.

Background: Most clinical data for multiple sclerosis are hospital based-that is, derived from patients referred to clinics specialising in the disease., Objectives: To present data derived from two population based multiple sclerosis populations, an incidence cohort and a prevalence population, from Västerbotten County, northern Sweden., Methods: The two populations were identified from multiple sources, and case ascertainment was assured through a personal clinical review, including interviews and examination of the patients., Results: Characteristics at onset for the different clinical subtypes of multiple sclerosis are presented, including the clinical spectrum of the first attack, the anatomical correlation between the first and second attacks, sex distribution, and disability distribution., Conclusions: Based on the comparison of present and earlier natural history data, multiple sclerosis appears to be a slightly more benign disease than previously recognised.

The aims of this study of a cross-sectional multiple sclerosis (MS) population in Västerbotten County, northern Sweden, were to estimate the prevalence of sick leave, professional assistance and housing; to study risk factors for sick leave; and to estimate the odds for sick leave in comparison with the general population of the county. The consequences of MS-related incapacity on the socioeconomic factors studied were considerable. Almost half (45%) of prevalent MS cases aged 18-64 years were fully sick listed and only one-third (35%) were not sick listed at all. Every fourth individual in the prevalence population received professional assistance, and 9% were living in care homes or special apartments for the disabled. Multiple logistic regression analysis identified the Expanded Disability Status Scale (EDSS) as the strongest predictor of sick leave. The time from symptom onset to full sick leave leading to temporary or permanent disability pension was significantly shorter for cases with progressive onset, higher age at onset and in males. The risk of full sick leave due to MS was six times higher than in the general population.

Objective: To investigate the incidence and prevalence of multiple sclerosis in Västerbotten County in northern Sweden., Methods: Multiple sources were used in the case identification process. Follow up interviews with clinical examinations were undertaken and, when indicated, additional paraclinical investigations were done. In this way case ascertainment was assured and supplemental clinical data were collected. The incidence rate was based on symptom onset. Onset adjusted prevalence was applied., Results: The crude incidence rate of multiple sclerosis in 1988-97 in Västerbotten County was 5.2/10(5) (95% confidence interval, 4.4 to 6.2): 6.7/10(5) (6.0 to 8.3) in women and 3.7/10(5) (2.7 to 4.9) in men. The onset adjusted prevalence for 31 December 1997 was 154/10(5) (139 to 170): 202/10(5) (179 to 228) in women and 105/10(5) (89 to 125) in men. When compared with a previous estimate of prevalence, a yearly 2.6% increase in prevalence between 1990 and 1997 was found, mainly attributable to a higher incidence than mortality., Conclusions: The present incidence rate and prevalence confirms earlier findings that Västerbotten is a high risk area for multiple sclerosis. The adjusted incidence was twice as high as the incidence from 1974-88 in the only previous Swedish population based study from Göteborg, but comparable with other recent Fennoscandian multiple sclerosis incidence rates.

Objective: To estimate the prevalence and clinical characteristics of multiple sclerosis (MS) in Västerbotten County in northern Sweden., Methods: Individuals with MS were identified from several sources. A follow-up interview and/or examination was performed in 94% of cases still living in the area during 1997-99. Onset adjusted prevalence and a definition of onset symptoms were applied., Results: A total of 313 cases were identified, resulting in an onset adjusted crude prevalence of MS for January 1990 of 125/105 (95% confidence interval (CI): 112-140). Female predominance was evident (163/105 (95% CI: 142-187) vs 86/105 (95% CI: 71-104)). Diagnostic coding registers were the most important source for identification of cases., Conclusions: The crude prevalence of MS in Västerbotten was higher than previous reports from other major areas in Scandinavia. The adjusted prevalence was significantly higher when compared with a previous study from Göteborg, south-western Sweden. The methodology used in this study gives a high degree of case ascertainment and increases the comparability of multiple sclerosis epidemiological studies.

Background: Most clinical data for multiple sclerosis are hospital based-that is, derived from patients referred to clinics specialising in the disease. Objectives: To present data derived from two population based multiple sclerosis populations, an incidence cohort and a prevalence population, from Vasterbotten County, northern Sweden. Methods: The two populations were identified from multiple sources, and case ascertainment was assured through a personal clinical review, including interviews and examination of the patients. Results: Characteristics at onset hr the different clinical subtypes of multiple sclerosis are presented, including the clinical spectrum of the first attack, the anatomical correlation between the first and second attacks, sex distribution, and disability distribution. Conclusions: Based on the comparison of present and earlier natural history data, multiple sclerosis appears to be a slightly more benign disease than previously recognised. [ABSTRACT FROM AUTHOR]