Cecilia Ahlgren

High nationwide prevalence of multiple sclerosis in Sweden.

Background: Few nationwide multiple sclerosis (MS) prevalence studies have been published. In Scandinavia, the nationwide MS prevalence was 173/100,000 in Denmark 2005 and 100/100,000 in Iceland 1990. Objective: Our aim with the present study was to determine the first population-based nationwide MS prevalence in Sweden, based on observed, registered patients and to investigate the presence of a north–south gradient of MS prevalence. Methods: By linking the Swedish National Patient Register, the Swedish Multiple Sclerosis Registry and the Swedish Total Population Register we obtained the number of patients who were diagnosed with MS before 2009, and who were registered, alive and resident in Sweden on the prevalence date 31 December 2008. We calculated the gender-specific nationwide MS prevalence in 1-year age intervals. The relationship between MS risk and latitude was studied in a logistic regression model including all individuals in the population of Sweden. Results: The number of registered MS patients in 2008 was 17,485 out of the Swedish population of 9,256,347. The overall MS prevalence was 188.9/100,000 (95% CI 186.1–191.7), 113.4 (95% CI 110.3–116.5) for men and 263.6 (95% CI 258.9–268.3) for women. The female to male ratio was 2.35:1. The prevalence of MS significantly increased for each degree of north latitude with 1.5% in men (p = 0.013) and 1% in women (p = 0.015). Conclusions: The MS prevalence of 188.9/100,000 in Sweden is among the highest nationwide prevalence estimates in the world. In Sweden, the risk of MS increases with increasing north latitude for both men and women.

Multiple sclerosis incidence in the era of measles-mumps-rubella mass vaccinations

Background –  Viral childhood infections may be involved in the multiple sclerosis (MS) pathogenesis. Following national Swedish vaccination programs, measles sharply declined in the 1970s, and measles, mumps, and rubella were virtually eliminated in cohorts born from 1981.

A population-based case―control study on viral infections and vaccinations and subsequent multiple sclerosis risk

Viral infections are probably involved in the pathogenesis of multiple sclerosis (MS). A recent cohort study in the Gothenburg population revealed no change in MS incidence associated with the introduction of the Swedish measles, mumps and rubella vaccination programmes. The aim of the present study was to clarify whether these infections or vaccinations, and two other infections, varicella and infectious mononucleosis, influence MS risk. We performed a population-based case–control study in Gothenburg that included 509 MS cases and 2,067 controls, born 1959–1986. Data on infections and vaccinations were obtained from questionnaires and from child health and school health records. We found no significant associations between measles, mumps, rubella or varicella and MS risk. These results were consistent between the two source materials. Infectious mononucleosis was associated with significantly higher MS risk (odds ratio 2.03, 95% CI 1.52–2.73). Overall, there was no significant association between measles-mumps-rubella (MMR) vaccination and MS risk, while those MMR vaccinated before age ten only were at significantly higher MS risk (odds ratio 4.92, 95% CI 1.97–12.20). Those MMR vaccinated both before and after age ten had intermediate MS risk. Infection with measles, mumps, rubella and varicella did not influence MS risk in contrast to infectious mononucleosis which conferred doubled MS risk. The association with ‘early’ MMR vaccination only was an isolated finding, limited by a small number of subjects and multiple testing. Most likely this was a chance finding. Future studies could investigate it on an a priori basis.

A nationwide survey of the prevalence of multiple sclerosis in immigrant populations of Sweden.

Background: In 2008, immigrants constituted 14% of the population of Sweden, a high-risk area for multiple sclerosis (MS). We investigated the largest Swedish immigrant populations for the prevalence of MS. Method: Data on foreign-born MS patients were retrieved from Swedish national health and population registers. We calculated observed versus expected numbers of MS patients and gender- and age-specific prevalence ratios (PR) between immigrant populations and the general population of Sweden and, where possible, of the countries of birth. Results: The 19 largest immigrant populations included 1327 MS patients. The global variation in MS prevalence was reflected in Sweden. The prevalence in immigrant populations who had moved to Sweden from countries with a lower MS risk was however higher than in their countries of birth. Notably, the MS prevalence in the population born in Iran was at least as high as in the general population of Sweden (men: PR = 1.10, 95% CI 0.81–1.46, p = 0.537, women: PR = 1.18, 95% CI 0.97–1.44, p = 0.855) and more than twice as high as in Isfahan, Iran (men: PR = 3.06 (95% CI 2.26–4.06), p <0.001, women: PR = 2.21 (95% CI 1.81–2.68), p <0.001). Conclusions: The MS prevalence increased in migrants who moved to Sweden from countries with a lower MS risk. In the Iranian immigrant population the prevalence exceeded that in the general population of Sweden. This indicates that Iranians carry genetic factors that contribute to a higher MS risk when environmental–lifestyle MS risk factors change.

High Nationwide Incidence of Multiple Sclerosis in Sweden

Over recent years increased MS incidence, primarily in women, has been reported. We recently reported an unexpectedly high MS prevalence of 189/100,000 in Sweden. In the present study we estimated the nationwide age- and gender-specific MS incidence and the sex ratio in Sweden between 2001 and 2008. MS patients were identified by linking two nationwide health data registers, and the Swedish population register. The earliest registered date of MS diagnosis was determined. By logistic regression, the probability of the date of MS diagnosis being within the incidence period, depending on age and time was estimated for a subset of patients and applied to other patients. By Poisson regression, the hazard functions for the incidence of MS diagnosis were estimated. The expected number of MS patients was 7,361.4. The incidence in the average population of 9,054,658 was 10.2 per 100,000 person-years, and 6.2 and 14.0 per 100,000 person-years for men and women, respectively. The crude female to male ratio was 2.26. No increase of incidence or change of sex ratio was observed from 2001 to 2008. In conclusion, the average MS incidence in Sweden from 2001 to 2008 was 10.2 per 100.000, which was considerably higher than previous regional Swedish estimates of 4.3–6.4. No increase of female to male ratio of MS during the study period was observed. We provide supplementary data that can be used as tools for examining excess MS risk in different study materials.

High risk of MS in Iranian immigrants in Gothenburg, Sweden

Background: In this study we investigated the risk of multiple sclerosis (MS) in migrants who had moved from Iran to Gothenburg, Sweden. Methods: Patients born in Iran were retrieved from a population-based cohort, which included 534 MS and clinically isolated syndrome patients, born 1959—1990, aged 10—39 years at disease onset in Gothenburg. The expected versus observed number of migrants from Iran was calculated. Results: The MS risk in the Iranian migrants in Gothenburg was several times higher than in Isfahan, Iran (hazard ratio 3.88, 95% confidence interval 2.17—6.40). Compared with the general population of Gothenburg, the observed number of 17 Iranian patients was higher than the expected value of 9.89 (hazard ratio 1.72, 95% confidence interval 1.00—2.75). Conclusion: Migration from a medium-risk to a high-risk area may increase the MS risk to that of the high-risk area.

Serum and CSF measles antibody levels increase over time in patients with multiple sclerosis or clinically isolated syndrome

In general, measles virus (MV) immunoglobulin G (IgG) antibody titres decline over time. However, we found that serum and CSF MV antibody titres increased with age (slope=0.038, p<0.001 and slope=0.022, p=0.008), respectively, and disease duration (slope=0.031, p=0.002 and slope=0.032, p=0.005), respectively, in patients with multiple sclerosis (MS) or clinically isolated syndrome (CIS). The age dependency of serum antibody levels differed between patients and controls (slope=0.038 versus -0.004, p<0.001). The increasing MV antibody titres over time in MS/CIS patients support a general nonspecific stimulation of B cells and plasma cells that is not confined only to the CNS/CSF compartment.

The effect of live, attenuated measles vaccine and measles infection on measles antibody levels in serum and CSF of patients with multiple sclerosis or clinically isolated syndrome.

High occurrence of measles, rubella and varicella zoster antibodies has been used as a biomarker for MS (the MRZ test). We analyzed measles antibody titres with respect to measles infection/measles vaccination status in 166 patients with MS or clinically isolated syndrome. Fifty blood donors served as controls. Measles vaccination yielded CSF measles antibodies in fewer patients (62%) than measles infection did (87%, p=0.001) and yielded lower measles titres in both serum and CSF (p<0.001). Controls had lower CSF measles titres than patients with measles vaccination alone (p<0.001). Childhood vaccinations probably reduce the sensitivity of the MRZ diagnostic test for MS.

Multiple sclerosis immunopathic trait and HLA-DR(2)15 as independent risk factors in multiple sclerosis

We analysed HLA haplotypes in pairs of 78 sporadic multiple sclerosis (MS) patients and 78 healthy siblings. The presence of 2 oligoclonal IgG bands, detected by immunoblotting of the cerebrospinal fluid in healthy siblings, has previously been defined as MS immunopathic trait (MSIT), based on a cut-off derived from healthy unrelated volunteers. The frequency of MSIT was 17.9% (n=14/78 siblings). The HLA-DR(15)2 allelle was present in 21.4% (n=3/14) of the siblings with MSIT, in 40.6% (n =26/64) of the siblings without MSIT, and in 59% (n =46/78) of the patients with clinically-definite (CD) MS. The distribution of zero, one or two HLA-DR(2)15 alleles was significantly skewed towards a lower allelle count in the siblings with MSIT compared with the group of unrelated siblings with MS (P=0.002), and also lower than their related siblings with MS (P=0.1). These results suggest that the MS susceptibility gene, HLA-DR(2)15 type, does not induce MSIT, and conceivably these are two separate risk factors in the development of MS. The effect of HLA-DR(2)15 and MSIT in sporadic MS appears to be synergistic. Multiple Sclerosis 2007; 13: 441-445. http://msj.sagepub.com

Sequence analysis of human rhinovirus aspirated from the nasopharynx of patients with relapsing-remitting MS

Background Upper respiratory infections were reported to trigger multiple sclerosis relapses. A relationship between picornavirus infections and MS relapses was recently reported. Objective To evaluate whether human rhinovirus is associated with multiple sclerosis relapses and whether any particular strain is predominant. Method Nasopharyngeal fluid was aspirated from 36 multiple sclerosis patients at pre-defined critical time points. Reverse-transcriptase-PCR was performed to detect human rhinovirus-RNA. Positive amplicons were sequenced. Results We found that rhinovirus RNA was present in 17/40 (43%) of specimens obtained at the onset of a URTI in 19 patients, in 1/21 specimens during convalescence after URTI in 14 patients, in 0/6 specimens obtained in 5 patients on average a week after the onset of an “at risk” relapse, occurring within a window in time from one week before to three weeks after an infection, and in 0/17 specimens obtained after the onset of a “not at risk” relapse not associated with any infection in 12 patients. Fifteen specimens from healthy control persons not associated with URTI were negative. The frequency of HRV presence in URTI was similar to that reported for community infections. Eight amplicons from patients represented 5 different HRV strains. Conclusion We were unable to reproduce previous findings of association between HRV infections and multiple sclerosis relapses. HRV was not present in nasopharyngeal aspirates obtained during “at risk” or “not at risk” relapses. Sequencing of HRV obtained from patients during URTI did not reveal any strain with predominance in multiple sclerosis.