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  • 1.
    Björnevik, Kjetil
    et al.
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Riise, Trond
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Boström, Inger
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Casetta, Ilaria
    University of Ferrara, Italy.
    Cortese, Marianna
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Granieri, Enrico
    University of Ferrara, Italy.
    Holmoy, Trygve
    University of Oslo, Norway; Akershus University Hospital, Norway.
    Kampman, Margitta T.
    University Hospital North Norway, Norway.
    Landtblom, Anne-Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken. Uppsala University, Sweden.
    Magalhaes, Sandra
    McGill University, Canada.
    Pugliatti, Maura
    University of Bergen, Norway; University of Ferrara, Italy.
    Wolfson, Christina
    McGill University, Canada; McGill University, Canada.
    Myhr, Kjell-Morten
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Negative interaction between smoking and EBV in the risk of multiple sclerosis: The EnvIMS study2017Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 23, nr 7, s. 1018-1024Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Results from previous studies on a possible interaction between smoking and Epstein-Barr virus (EBV) in the risk of multiple sclerosis (MS) are conflicting. Objectives: To examine the interaction between smoking and infectious mononucleosis (IM) in the risk of MS. Methods: Within the case-control study on Environmental Factors In Multiple Sclerosis (EnvIMS), 1904 MS patients and 3694 population-based frequency-matched healthy controls from Norway, Italy, and Sweden reported on prior exposure to smoking and history of IM. We examined the interaction between the two exposures on the additive and multiplicative scale. Results: Smoking and IM were each found to be associated with an increased MS risk in all three countries, and there was a negative multiplicative interaction between the two exposures in each country separately as well as in the pooled analysis (p=0.001). Among those who reported IM, there was no increased risk associated with smoking (odds ratio (OR): 0.95, 95% confidence interval (CI): 0.66-1.37). The direction of the estimated interactions on the additive scale was consistent with a negative interaction in all three countries (relative excess risk due to interaction (RERI): -0.98, 95% CI: -2.05-0.15, p=0.09). Conclusion: Our findings indicate competing antagonism, where the two exposures compete to affect the outcome.

  • 2.
    Bjørnevik, Kjetil
    et al.
    University of Bergen, Norway; Haukeland Hospital, Norway .
    Riise, Trond
    University of Bergen, Norway; Haukeland Hospital, Norway .
    Casetta, Ilaria
    University of Ferrara, Italy .
    Drulovic, Jelena
    University of Belgrade, Serbia .
    Granieri, Enrico
    University of Ferrara, Italy .
    Holmoy, Trygve
    University of Oslo, Norway; Akershus University Hospital, Norway .
    Kampman, Margitta T.
    University of Tromsø, Norway; University Hospital North Norway.
    Landtblom, Anne-Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Medicinska specialistkliniken .
    Lauer, Klaus
    Griesheim, Darmstadt, Germany.
    Lossius, Andreas
    University of Oslo, Norway; National Hospital Norway.
    Magalhaes, Sandra
    McGill University, Canada .
    Myhr, Kjell-Morten
    Haukeland Hospital, Norway; University of Bergen, Norway .
    Pekmezovic, Tatjana
    University of Belgrade, Serbia .
    Wesnes, Kristin
    University of Bergen, Norway; Haukeland Hospital, Norway .
    Wolfson, Christina
    McGill University, Canada .
    Pugliatti, Maura
    University of Bergen, Norway; University of Sassari, Italy .
    Sun exposure and multiple sclerosis risk in Norway and Italy: The EnvIMS study2014Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, nr 8, s. 1042-1049Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES:

    The objective of this paper is to estimate the association between multiple sclerosis (MS) and measures of sun exposure in specific age periods in Norway and Italy.

    METHODS:

    A total of 1660 MS patients and 3050 controls from Italy and Norway who participated in a multinational case-control study (EnvIMS) reported sun habits during childhood and adolescence.

    RESULTS:

    A significant association between infrequent summer outdoor activity and increased MS risk was found in Norway and in Italy. The association was strongest between the ages of 16 and 18 years in Norway (odds ratio (OR) 1.83, 95% confidence interval (CI) 1.30-2.59), and between birth and age 5 years in Italy (OR 1.56, 95% CI 1.16-2.10). In Italy a significant association was also found during winter (OR 1.42, 95% CI 1.03-1.97). Frequent sunscreen use between birth and the age of 6 years was associated with MS in Norway (OR 1.44, 95% CI 1.08-1.93) after adjusting for outdoor activity during the same period. Red hair (OR 1.67, 95% CI 1.06-2.63) and blonde hair (OR 1.36, 95% CI 1.09-1.70) were associated with MS after adjusting for outdoor activity and sunscreen use.

    CONCLUSION:

    Converging evidence from different measures underlines the beneficial effect of sun exposure on MS risk.

  • 3.
    Boström, Inger
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet.
    Callander, Margarita
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet.
    Kurtzke, John F
    Department of Neurology, Georgetown University, Washington, DC, USA.
    Landtblom, Anne-Marie
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Neurologi. Linköpings universitet, Hälsouniversitetet.
    High prevalence of multiple sclerosis in the Swedish county of Värmland2009Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 15, nr 11, s. 1253-1262Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Previous epidemiological studies have indicated that the county of Värmland in western Sweden may be a high-risk zone for multiple sclerosis (MS). The objective of this study was to determine the prevalence in the area. Hospital and general practice medical files were scrutinized. The diagnostic criteria of Poser were used, with 31 December 2002 as prevalence day. The prevalence was 170.07 per 100,000 inhabitants. The average annual incidence was 6.39 to 6.46 per 100,000 (1991—1995, 1996—2000). Multiple sclerosis was 2.3 times more common among women than men. There was a variation in prevalence among the 16 municipalities, however it was not statistically significant. The rates seemed highest in the southwestern part of the county, roughly similar in location to findings some 70 years earlier. When the prevalence ratios by geographical units for the county in 1933 were applied to the current prevalence, the distribution from these estimated cases differed from homogeneity with very high significance (p < 0.00001 ). In conclusion, this study supports previous reports indicating that Värmland continues to be a high-risk zone for MS and shares in the diffusion of the disease at the county level which we had presented for the country as a whole.

  • 4.
    Boström, Inger
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet.
    Stawiarz, Leszek
    Division of Neurology, Dept of Clinical Neuroscience, Karolinska Institute, STOCKHOLM, Sweden.
    Landtblom, Anne-Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Medicinska specialistkliniken .
    Sex ratio of multiple sclerosis in Sweden2013Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 13, nr 1, s. 46-52Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Sex ratio of multiple sclerosis has been reported from several areas. The disease is more common in women. In Europe the women-to-men ratio varies from 1.1 to 3.4. Recently a study in Canada has reported a significant increased female-to-male ratio in multiple sclerosis.

    Our objective was to analyse the development of sex ratio in multiple sclerosis in the Swedish population.

    Data from the Swedish MS Register and data from the Swedish National Statistics Office were used to estimate sex ratio by year of birth and year of onset.

    In analyse of sex ratio by year of birth there were 8,834 patients (6,271 women and 2,563 men) born during 1931 to 1985. The mean value of women-to-men ratio was 2.62. No clear trend was noted for the women-to-men ratio by year of birth (Spearman’s rho = 0.345, p=0.298, n=11). Patients analysed by year of onset was 9,098 (6,452 women and 2,646 men) during the study time period 1946 until 2005. The mean women-to-men ratio was 2.57. There was no significant change of the women-to-men ratio (Spearman’s rho = -0.007, p = 0.983, n = 12).

    Conclusion: In the Swedish patients there was no evidence for an increased womento-men ratio in multiple sclerosis.

  • 5.
    Brennan, R.M.
    et al.
    Queensland Institute for Medical Research.
    Burrows, J.M.
    Queensland Institute for Medical Research.
    Bell, M.J.
    Queensland Institute for Medical Research.
    Bromham, L.
    Australian National University.
    Csurhes, P.A.
    University of Queensland.
    Lenarczyk, A.
    University of Queensland.
    Sverndal, J.
    Linköpings universitet, Institutionen för hälsa och miljö. Linköpings universitet, Hälsouniversitetet.
    Klintenstedt, J.
    Linköpings universitet, Institutionen för hälsa och miljö. Linköpings universitet, Hälsouniversitetet.
    Pender, M.P.
    University of Queensland.
    Burrows, S.R.
    Queensland Institute for Medical Research.
    Strains of Epstein-Barr virus infecting multiple sclerosis patients2010Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 16, nr 6, s. 643-651Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Both epidemiological and experimental studies have indicated that the ubiquitous herpesvirus Epstein-Barr virus (EBV) plays a role in the pathogenesis of multiple sclerosis (MS). Some features of MS epidemiology, such as the decline in risk among migrants from high to low MS prevalence areas, suggest the presence of variant EBV strains that increase MS risk. The objective of this study was to investigate whether genetic variability in EBV is associated with MS. Genes encoding for two EBV antigens (EBNA1 and BRRF2) were sequenced in EBV isolates from 40 MS patients and a similar number of control subjects. These viral antigens were chosen for analysis because they are known to stimulate atypical immune responses in MS. Extensive sequence polymorphism was observed within the EBNA1 and BRRF2 genes in isolates from both MS patients and controls. Interestingly, several single nucleotide polymorphisms within the EBNA1 gene, and one within the BRRF2 gene, were found to occur at marginally different frequencies in EBV strains infecting MS patients versus controls. Although this study does not find a simple causal relationship between EBV strains and the occurrence of MS, the existence of haplotypes that occur at different frequencies in MS patients versus controls may provide an area for future study of the role of EBV strain variation in multiple sclerosis.

  • 6.
    Callander, Margarita
    et al.
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Neurologi. Linköpings universitet, Hälsouniversitetet.
    Haghighi, S.
    Institute of Clinical Neuroscience, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Landtblom, Anne-Marie
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Neurologi. Linköpings universitet, Hälsouniversitetet.
    Ahlgren, C. E.
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Nilsson, S. I.
    Department of Mathematical Statistics, Chalmers University of Technology, Gothenburg, Sweden.
    Rydberg, L.
    Department of Transplantation Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Al Khoury, H.
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Neurologi. Linköpings universitet, Hälsouniversitetet.
    Rosengren, L.
    Institute of Clinical Neuroscience, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Andersen, O.
    Gothenburg University, Gothenburg, Sweden.
    Multiple sclerosis immunopathic trait and HLA-DR(2)15 as independent risk factors in multiple sclerosis2007Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 13, nr 4, s. 441-445Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 7.
    Edström, Måns
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Mellergård, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Mjösberg, Jenny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Vrethem, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Press, R
    Huddinge University Hospital.
    Dahle, Charlotte
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Transcriptional characteristics of CD4+ T cells in multiple sclerosis: relative lack of suppressive populations in blood2011Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 17, nr 1, s. 57-66Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background:Multiple sclerosis (MS) is hypothetically caused by autoreactive Th1 and Th17 cells, whereas Th2 and regulatory T cells may confer protection. The development of Th subpopulations is dependant on the expression of lineage-specific transcription factors.

    Objective:The aim of this study was to assess the balance of CD4+T cell populations in relapsing-remitting MS.

    Methods:Blood mRNA expression of TBX21, GATA3, RORC, FOXP3 and EBI3 was assessed in 33 patients with relapsing-remitting MS and 20 healthy controls. In addition, flow cytometry was performed to assess T lymphocyte numbers.

    Results:In relapsing-remitting MS, diminished expression of FOXP3 (Treg) was found (p < 0.05), despite normal numbers of CD4+CD25hiTreg. Immunoregulatory EBI3 and Th2-associated GATA3 ([a-z]+) was also decreased in MS (p < 0.005 and p < 0.05, respectively). Expression of TBX21 (Th1) and RORC (Th17) did not differ between patients and controls. Similar changes were observed when analysing beta-interferon treated (n = 12) or untreated (n = 21) patients. Analysis of transcription factor ratios, comparing TBX21/GATA3 and RORC/FOXP3, revealed an increase in the RORC/FOXP3 ratio in patients with relapsing-remitting MS (p < 0.005).

    Conclusion:Our findings indicate systemic defects at the mRNA level, involving downregulation of beneficial CD4+phenotypes. This might play a role in disease development by permitting activation of harmful T cell populations.

  • 8.
    Granqvist, Mathias
    et al.
    Karolinska Inst, Sweden.
    Burman, Joachim
    Uppsala Univ, Sweden.
    Gunnarsson, Martin
    Orebro Univ, Sweden.
    Lycke, Jan
    Sahlgrens Univ Hosp, Sweden.
    Nilsson, Petra
    University Hospital, Lund, Sweden.
    Olsson, Tomas
    Karolinska Inst, Sweden.
    Sundstrom, Peter
    Skane Univ Hosp, Sweden; Umea Univ, Sweden.
    Svenningsson, Anders
    Karolinska Inst, Sweden.
    Vrethem, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Frisell, Thomas
    Karolinska Inst, Sweden.
    Piehl, Fredrik
    Karolinska Inst, Sweden.
    Comparative effectiveness of dimethyl fumarate as the initial and secondary treatment for MS2019Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, artikel-id UNSP 1352458519866600Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Population-based real-world evidence studies of the effectiveness and tolerability of dimethyl fumarate in relation to common treatment alternatives are still limited. Objective: To evaluate the clinical effectiveness and tolerability of dimethyl fumarate (DMF) as the initial and secondary treatment for relapsing-remitting multiple sclerosis (RRMS) patients compared with common treatment alternatives in Sweden. Methods: We conducted a nationwide retrospective observational cohort study of all RRMS patients identified through the Swedish MS registry initiating DMF (n = 641) or interferons/glatiramer acetate (IFN/GA; n = 555) as the initial therapy, or DMF (n = 703) or fingolimod (FGL; n = 194) after switch from IFN/GA between 1 January 2014 and 31 December 2016. Results: The discontinuation rate was lower with DMF as the initial treatment than IFN/GA (adjusted hazard rate (HR): 0.46, 95% confidence interval (CI): 0.37-0.58, p amp;lt; 0.001), but higher than FGL as the secondary treatment (HR: 1.51, CI: 1.08-2.09, p amp;lt; 0.05). Annualized relapse rate (ARR) was lower with DMF compared to IFN/GA (0.04, CI: 0.03-0.06 vs 0.10, CI: 0.07-0.13; p amp;lt; 0.05), but not FGL (0.03, CI: 0.02-0.05 vs 0.02, CI: 0.01-0.04; p = 0.41). Finally, time to first relapse (TTFR) was longer with DMF as the initial, but not secondary, therapy (p amp;lt; 0.05 and p = 0.20, respectively). Conclusion: Our findings indicate that DMF performs better than IFN/GA as the initial treatment for RRMS. Compared to FGL, DMF displayed a lower tolerability, but largely similar effectiveness outcomes.

  • 9.
    Holmen, Carolina
    et al.
    Karolinska Institutet.
    Piehl, Fredrik
    Karolinska Institutet.
    Hillert, Jan
    Karolinska Institutet.
    Fogdell-Hahn, Anna
    Karolinska Institutet.
    Lundkvist, Malin
    Karolinska Institutet.
    Karlberg, Elin
    Karolinska Institutet.
    Nilsson, Petra
    Skanes University Sjukhus.
    Dahle, Charlotte
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Feltelius, Nils
    Med Prod Agcy, Uppsala.
    Svenningsson, Anders
    Umea University.
    Lycke, Jan
    University of Gothenburg.
    Olsson, Tomas
    Karolinska Institute.
    A Swedish national post-marketing surveillance study of natalizumab treatment in multiple sclerosis2011Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 17, nr 6, s. 708-719Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: A post marketing surveillance study was conducted to evaluate safety and efficacy of natalizumab in Swedish multiple sclerosis (MS) patients since its introduction in August 2006 until March 2010. Methods: Patients were registered in the web-based Swedish MS-registry at 40 locations and evaluated every 6 months. Adverse events and clinical outcomes were recorded. Results: One thousand one hundred and fifty-two patients were included (71.4% female) and 149 patients stopped treatment; the main reason was planned pregnancy. Anti-natalizumab antibodies were found in 4.5% (52 patients) of which 1.6% displayed persistent antibodies. Serious adverse events were rare, but included three cases with progressive multifocal leukoencephalopathy (PML). There were seven fatal cases, probably unrelated to the natalizumab treatment. For relapsing-remitting MS patients (n = 901), mean Expanded Disability Status Scale (EDSS, -10.7%), Multiple Sclerosis Severity Scale (MSSS, -20.4%), Multiple Sclerosis Impact Scale (MSIS-29, physical -9.9%, psychological -13.3%) and Symbol Digit Modalities Test (SDMT, +10.7%) all showed significant improvements during 24 months of treatment with natalizumab. The Swedish web-based MS quality registry proved to function as a platform for post-marketing MS drug surveillance, providing long-term data regarding drug effects and adverse events beyond clinical trials. Conclusions: Our results indicate that natalizumab is generally well tolerated and has sustained efficacy for patients with active MS, though the risk of PML is still an important concern.

  • 10.
    Jansson, A.
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Kvarnström, Maria
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Ekerfelt, Christina
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Vrethem, Magnus
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Neurologi. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Neurofysiologi.
    Elispot assay detection of cytokine secretion in multiple sclerosis patients treated with interferon-β1a or glatiramer acetate compared with untreated patients2003Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 9, nr 5, s. 440-445Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The mechanisms behind the beneficial effects of interferon-β1a (IFN-β1a) and glatiramer acetate (GA) in the treatment of multiple sclerosis (MS) are still uncertain. Altered cytokine patterns have been suggested including inhibition of proinflammatory cytokines like interferon-γ (IFN-γ) and enhancement of anti-inflammatory cytokines such as interleukin-4 (IL-4). Twenty-nine patients with MS (10 untreated, nine treated with IFN-β1a and 10 with GA) were investigated with elispot of peripheral blood mononuclear cells. Spontaneous and myelin induced (myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG)-14-39 and MOG 63-87) IFN-γ, IL-4, IL-5 and IL-10 secretion was studied. We found a significant reduction of spontaneous IFN-γ, IL-4 and IL-5, but no difference in IL-10 secreting cells in both groups of treated patients compared with the untreated patients. Myelin-specific responses showed a significant decrease of IFN-γ and an increase of IL-5, but no change in IL-4 and IL-10 secreting cells in treated compared with untreated patients. Both treatment groups revealed similar cytokine secretion patterns except for a more pronounced decrease of both spontaneous and MOG 14-39 induced IL-4 secretion in the IFN-β1a treated group. Thus, immunological effects of IFN-β1a and GA were similar showing that disease promoting Th1 (IFN-γ) cells were reduced while the potentially beneficial Th2 response (IL-4) was maintained.

  • 11.
    Landtblom, Anne-Marie
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Jaworski, Jacek
    Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Dahlqvist Leinhard, Olof
    Linköpings universitet, Institutionen för medicin och vård, Radiofysik. Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US.
    Gustafsson, Maria C.
    Linköpings universitet, Institutionen för medicin och vård, Radiofysik.
    Lundberg, Peter
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US.
    Absolute metabolite concentrations in cerebral white matter of multiple sclerosis patients with beta interferon treatment2008Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 14, nr Suppl. 1, s. S162-S162Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: A few investigations concern interferon (IFN)-treated multiple sclerosis (MS) patients using proton spectroscopy, however not with an absolute quantitation or during extended treatment.

    Objective: To quantify metabolite changes during IFN therapy using magnetic resonance spectroscopy.

    Methods: We included 14 MS patients, (9 men, 5 women, mean age 41.8 years, mean disease duration 10.9 years, 9 with relapsing-remitting MS, 6 with secondary progressive and bouts) scheduled for immunomodulatory treatment (5 IFN1A, 9 IFN1B) as well as 14 healthy controls, (8 men, 6 women, mean age 40.2 years). All patients had clinically definite MS (Poser criteria). Measurements were performed in white matter (four voxels).

    Results: Longitudinal results: N-acetylaspartate + Nacetylapartylglutamate (NAA+NAAG) showed a trend to higher values before treatment. Myo-inositol concentrations were significantly and increasingly elevated (p=0.03). Glutamine and glutamate concentrations dropped significantly (p=0.009) after treatment started but raised later. MS patients/ healthy controls: Creatine and myo-inositol concentrations were significantly higher in MS patients before and after treatment. NAA + NAAG concentrations were significantly lower before and after treatment. Glutamine and glutamate concentrations were higher before therapy, later equal to healthy controls.

    Conclusions: IFN-treated patients demonstrate increasing myoinositol, a marker of progressive glial proliferation. Also, decreasing concentrations of total NAA derivatives despite IFN therapy suggest ongoing progressive pathology and constant neuronal loss in the course of MS. MS patients compared with matched healthy controls show highly significant differences regarding metabolites (Cr, myo- Ins, NAA) that increase during the therapy period, also indicating that the medication can only moderately influence the metabolites. The most interesting finding is related the excitatory molecules, glutamine and glutamate. Before IFN therapy statistical analysis showed significant elevation in the concentrations; however after IFN therapy this difference is no longer observed. This finding underlines a possible role of IFN in the expression of down-regulating excitotoxic molecules.

  • 12.
    Lossius, Andreas
    et al.
    University of Oslo, Norway National Hospital Norway, Norway .
    Riise, Trond
    University of Bergen, Norway .
    Pugliatti, Maura
    University of Bergen, Norway University of Sassari, Italy .
    Bjornevik, Kjetil
    University of Bergen, Norway .
    Casetta, Ilaria
    University of Ferrara, Italy .
    Drulovic, Jelena
    University of Belgrade, Serbia .
    Granieri, Enrico
    University of Ferrara, Italy .
    Kampman, Margitta T.
    University of Tromso, Norway University Hospital North Norway, Norway .
    Landtblom, Anne-Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Medicinska specialistkliniken .
    Lauer, Klaus
    Griesheim, Germany.
    Magalhaes, Sandra
    McGill University, Canada .
    Myhr, Kjell-Morten
    Haukeland Hospital, Norway University of Bergen, Norway .
    Pekmezovic, Tatjana
    University of Belgrade, Serbia .
    Wesnes, Kristin
    University of Bergen, Norway .
    Wolfson, Christina
    McGill University, Canada McGill University, Canada .
    Holmoy, Trygve
    University of Oslo, Norway Aker University Hospital, Norway .
    Season of infectious mononucleosis and risk of multiple sclerosis at different latitudes; the EnvIMS Study2014Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, nr 6, s. 669-674Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Seasonal fluctuations in solar radiation and vitamin D levels could modulate the immune response against Epstein-Barr virus (EBV) infection and influence the subsequent risk of multiple sclerosis (MS). Methods: Altogether 1660 MS patients and 3050 controls from Norway and Italy participating in the multinational case-control study of Environmental Factors In Multiple Sclerosis (EnvIMS) reported season of past infectious mononucleosis (IM). Results: IM was generally reported more frequently in Norway (p=0.002), but was associated with MS to a similar degree in Norway (odds ratio (OR) 2.12, 95% confidence interval (CI) 1.64-2.73) and Italy (OR 1.72, 95% CI 1.17-2.52). For all participants, there was a higher reported frequency of IM during spring compared to fall (pless than0.0005). Stratified by season of IM, the ORs for MS were 1.58 in spring (95% CI 1.08-2.31), 2.26 in summer (95% CI 1.46-3.51), 2.86 in fall (95% CI 1.69-4.85) and 2.30 in winter (95% CI 1.45-3.66). Conclusions: IM is associated with MS independently of season, and the association is not stronger for IM during spring, when vitamin D levels reach nadir. The distribution of IM may point towards a correlation with solar radiation or other factors with a similar latitudinal and seasonal variation.

  • 13.
    Mellergård, Johan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Edström, Måns
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Vrethem, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Dahle, Charlotte
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Natalizumab treatment in multiple sclerosis: marked decline of chemokines and cytokines in cerebrospinal fluid2010Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 16, nr 2, s. 208-217Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Natalizumab exerts impressive therapeutic effects in patients with multiple sclerosis (MS). The proposed main mode of action is reducing transmigration of leukocytes into the CNS, but other immunological effects may also be operative. Cytokines and chemokines are involved in the regulation of inflammatory responses and may reflect the disease process in MS. The objective of this study was to evaluate the effects of natalizumab treatment on cytokine and chemokine profiles systemically and intrathecally in multiple sclerosis. We used luminex to analyse a panel of cytokines (IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, TNF-alpha, IFN-gamma, GM-CSF) and chemokines (CXCL9, CXCL10, CXCL11, CCL17, CCL22) in blood and cerebrospinal fluid (CSF) from 31 patients with relapsing MS before and after one year of natalizumab treatment. There was a marked decline in CSF levels of cytokines and chemokines, thus including pro-inflammatory cytokines (IL-1 beta, IL-6 and IL-8) as well as chemokines associated with both Th1 (CXCL9, CXCL10, CXCL11) and Th2 (CCL22). Circulating plasma levels of some cytokines (GM-CSF, TNF-alpha, IL-6 and IL-10) also decreased after one year of treatment. This is the first study to show that natalizumab treatment is associated with a global decline in cytokine and chemokine levels at a protein level. This finding was most pronounced in CSF, in line with the reduced transmigration of cells into CNS, whereas reduction in plasma levels indicates other possible mechanisms of natalizumab treatment.

  • 14. Nortvedt, MW
    et al.
    Riise, T
    Myhr, K-M
    Landtblom, Anne-Marie
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Bakke, A
    Nyland, H I
    Reduced guality of life among multiple sclerosis patients with sexual disturbance and bladder dysfunction2001Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 7, s. 231-235Artikel i tidskrift (Refereegranskat)
  • 15.
    Tedeholm, H
    et al.
    Sahlgrens University Hospital, Sweden .
    Lycke, J
    Sahlgrens University Hospital, Sweden .
    Skoog, B
    Sahlgrens University Hospital, Sweden .
    Lisovskaja, V
    Chalmers, Sweden .
    Hillert, J
    Karolinska University Hospital, Sweden .
    Dahle, Charlotte
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Fagius, J
    Karolinska University Hospital, Sweden .
    Fredrikson, S
    Karolinska University Hospital, Sweden .
    Landtblom, Anne-Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Malmestrom, C
    Sahlgrens University Hospital, Sweden .
    Martin, C
    University Hospital, Sweden .
    Piehl, F
    Karolinska University Hospital, Sweden .
    Runmarker, B
    Sahlgrens University Hospital, Sweden .
    Stawiarz, L
    Karolinska University Hospital, Sweden .
    Vrethem, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Nerman, O
    Chalmers, Sweden .
    Andersen, O
    Sahlgrens University Hospital, Sweden .
    Time to secondary progression in patients with multiple sclerosis who were treated with first generation immunomodulating drugs2013Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, nr 6, s. 765-774Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: It is currently unknown whether early immunomodulatory treatment in relapsing-remitting MS (RRMS) can delay the transition to secondary progression (SP). less thanbrgreater than less thanbrgreater thanObjective: To compare the time interval from onset to SP in patients with RRMS between a contemporary cohort, treated with first generation disease modifying drugs (DMDs), and a historical control cohort. less thanbrgreater than less thanbrgreater thanMethods: We included a cohort of contemporary RRMS patients treated with DMDs, obtained from the Swedish National MS Registry (disease onset between 1995-2004, n = 730) and a historical population-based incidence cohort (onset 1950-64, n = 186). We retrospectively analyzed the difference in time to SP, termed the "period effect" within a 12-year survival analysis, using Kaplan-Meier and Cox regression analysis. less thanbrgreater than less thanbrgreater thanResults: We found that the "period" affected the entire severity spectrum. After adjusting for onset features, which were weaker in the contemporary material, as well as the therapy initiation time, the DMD-treated patients still exhibited a longer time to SP than the controls (hazard ratios: men, 0.32; women, 0.53). less thanbrgreater than less thanbrgreater thanConclusion: Our results showed there was a longer time to SP in the contemporary subjects given DMD. Our analyses suggested that this effect was not solely driven by the inclusion of benign cases, and it was at least partly due to the long-term immunomodulating therapy given.

  • 16.
    Vrethem, Magnus
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Neurologi. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Fernlund, Ingrid
    Ernerudh, Jan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Öhman, Sten
    Prognostic value of cerebrospinal fluid IgA and IgG in multiple sclerosis2004Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 10, nr 4, s. 469-471Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    IgA antibodies do not activate complement and may compete with and protect against myelin degradation caused by IgM and IgG in multiple sclerosis (MS). We retrospectively evaluated cerebrospinal fluid (CSF) IgA and IgG (as indices and extended indices) from 1980 to 1988 in 68 patients with definitive MS. Sixty-one of them had survived since the time of sampling (11 - 19 years). IgA Extended Index was significantly higher for surviving patients (median 0.65) than for the dead patients (median 0.33). CSF IgA or IgG indices did not correlate with disability, walking distance, or time from onset of symptoms to the need of walking aid. The retrospective experimental design allowed an unusually long follow-up time, but it also had the disadvantages of such a study. Thus the results warrant a prospective study to verify the prognostic vale of CSF IgA in MS.

  • 17.
    Vrethem, Magnus
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Kvarnström, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Stenstam, J
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Cassel, Petra
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Gustafsson, M
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet.
    Landtblom, Anne-Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Medicinska specialistkliniken .
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Cytokine mapping in cerebrospinal fluid and blood in multiple sclerosis patients without oligoclonal bands2012Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 18, nr 5, s. 669-673Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Since there are clinical and genetic differences between MS patients with intrathecal oligoclonal bands (OCB+ ) in the cerebrospinal fluid (CSF) compared with those without (OCB-), the aim was to find out if OCB- patients showed a different pattern of cytokine immune activation compared with OCB+ patients. Methods: The study included 25 MS patients (10 OCB- and 15 OCB+ ) and 13 controls. A panel of cytokines was measured; IL-1β, IL-6, IL-8/CXCL8, IL-10, TNF and GM-CSF in serum, CSF and in supernatants from polyclonally stimulated blood mononuclear cells, where also levels of IL-12p40, IL-13, IL-15, IL-17 and IFN-γ were measured. The concentrations of soluble (s) VCAM-1 and sCD14 were measured in serum and CSF. Results: In general, there were no extensive differences in cytokine concentrations between the OCB- and OCB+ groups. Conclusion: OCB- MS patients do not seem to constitute a separate entity concerning inflammatory parameters measured as cytokine concentrations in CSF and blood.

  • 18.
    Vrethem, Magnus
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Mattsson, E
    Hebelka, H
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan.
    Leerbeck, K
    Österberg, A
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Landtblom, Anne-Marie
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Balla, B
    Motala.
    Nilsson, H
    Norrköping.
    Hultgren, M
    Jönköping.
    Brattström, L
    Kalmar.
    Kågedal, Bertil
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Increased plasma homocysteine levels without signs of vitamin B12 deficiency in patients with multiple sclerosis assessed by blood and cerebrospinal fluid homocysteine and methylmalonic acid2003Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 9, nr 3, s. 239-245Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: The aim of this study was to evaluate if multiple sclerosis (MS) is associated with vitamin B12 (cobalamin) deficiency. Methods: We measured serum vitamin B12, plasma folate, serum methylmalonic acid (MMA), plasma homocysteine (tHcy) and also cerebrospinal fluid (CSF) MMA and tHcy in 72 patients with MS and 23 controls. Results: The mean plasma tHcy level was significantly increased in MS patients (11.6 ╡mol/L) compared with controls (7.4╡mol/L) (P = 0.002). Seven patients showed low serum vitamin B12 levels but only one of them had concomitant high plasma tHcy. None of them showed high serum MMA. Plasma or blood folate levels did not differ between MS patients and controls. We found no significant differences in mean values or frequency of pathological tests of serum B12, serum MMA, mean corpuscular volume (MCV), haemoglobin concentration, CSF tHcy or CSF MMA between patients and healthy subjects. There were no correlations between CSF and serum/plasma levels of MMA or tHcy. Serum vitamin B12, serum MMA, plasma tHcy, CSF Hey or CSF MMA were not correlated to disability status, activity of disease, duration of disease or age. Conclusions: The relevance of the increased mean value of plasma tHcy thus seems uncertain and does not indicate functional vitamin B12 deficiency. We can not, however, exclude the possibility of a genetically induced dysfunction of the homocysteine metabolism relevant for the development of neuroinflammation/degeneration. Our findings indicate that, regardless of a significant increase in plasma tHcy in MS patients, the MS disease is not generally associated with vitamin B12 deficiency since we did not find any other factors indicating vitamin B12 deficiency. Analysis of CSF MMA and CSF tHcy, which probably reflects the brain vitamin B12 status better than serum, are not warranted in MS. We conclude that B12 deficiency, in general, is not associated with MS.

  • 19.
    Wesnes, Kristin
    et al.
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Myhr, Kjell-Morten
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Riise, Trond
    Haukeland Hosp, Norway; Univ Bergen, Norway.
    Cortese, Marianna
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Pugliatti, Maura
    Univ Bergen, Norway; Univ Ferrara, Italy.
    Boström, Inger
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Landtblom, Anne-Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken. Uppsala Univ, Sweden.
    Wolfson, Christina
    McGill Univ, Canada.
    Bjornevik, Kjetil
    Haukeland Hosp, Norway; Univ Bergen, Norway.
    Physical activity is associated with a decreased multiple sclerosis risk: The EnvIMS study2018Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, nr 2, s. 150-157Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The lifestyle factors smoking and obesity have been associated with the risk of multiple sclerosis (MS). Physical activity (PA) may also be of importance. Objective: To examine the association between PA and MS risk in Italy, Norway, and Sweden and to evaluate the possible influence by established risk factors. Methods: In this case-control study, 1904 cases and 3694 controls were asked to report their average weekly amounts of light and vigorous PA during adolescence on a scale ranging from none to more than 3 hours activity. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) and adjusted for potential confounders. Results: Vigorous PA was inversely associated with MS risk in the pooled analysis (p-trend amp;lt; 0.001) with an age-and sex-adjusted OR of 0.74 (95% CI: 0.63-0.87) when comparing the highest and lowest levels. Adjusting for outdoor activity, infectious mononucleosis, body size, and smoking yielded similar results. The association was present in all countries and was not affected by exclusion of patients with early disease onset. Light PA was not associated with the risk of MS. Conclusion: Our findings suggest that vigorous PA can modify the risk of developing MS independent of established risk factors.

  • 20.
    Wesnes, Kristin
    et al.
    University of Bergen/The Norwegian MS Competence Centre, Haukeland University Hospital, Norway .
    Riise, Trond
    University of Bergen/The Norwegian MS Competence Centre, Haukeland University Hospital, Norway.
    Casetta, Ilaria
    Section of Clinical Neurology, University of Ferrara, Italy.
    Drulovic, Jelena
    Clinic of Neurology, Faculty of Medicine, University of Belgrade, Serbia.
    Granieri, Enrico
    Section of Clinical Neurology, University of Ferrara, Italy.
    Holmøy, Trygve
    Institute of Clinical Medicine, Faculty of Medicine, University of Oslo/Akershus University Hospital, Norway.
    Kampman, Margitta T
    University of Tromsø/University Hospital of North Norway, Norway.
    Landtblom, Anne-Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Lauer, Klaus
    Darmstadt, Germany.
    Lossius, Andreas
    Institute of Clinical Medicine, Faculty of Medicine, University of Oslo/Institute of Immunology, Oslo University .
    Magalhaes, Sandra
    Department of Epidemiology and Biostatistics and occupational health, McGill University, Montreal, Canada.
    Pekmezovic, Tatjana
    Institute of Epidemiology, Faculty of Medicine, University of Belgrade, Serbia.
    Bjørnevik, Kjetil
    University of Bergen/The Norwegian MS Competence Centre, Haukeland University Hospital, Norway.
    Wolfson, Christina
    Research institute of the McGill University Health Centre, Montreal, Canada.
    Pugliatti, Maura
    University of Bergen, Norway/ Department of Clinical and Experimental Medicine, University of Sassari, Italy.
    Myhr, Kjell-Morten
    The Norwegian MS Competence Centre, Haukeland University Hospital/The KG Jebsen Centre for MS-Research, University of Bergen, Norway.
    Body size and the risk of multiple sclerosis in Norway and Italy: The EnvIMS study.2015Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, nr 4, s. 388-395Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Obesity may be a risk factor for developing multiple sclerosis (MS).

    OBJECTIVE: We examined if body size influences the risk of MS in a population-based, case control study.

    METHODS: A total of 953 cases and 1717 controls from Norway and 707 cases and 1333 controls from Italy reported their body size by choosing a silhouette 1 to 9 (largest) every fifth year from age 5 to 30 and at time of study. The body size-related MS risk was defined by odds ratios (ORs) in logistic regression analyses adjusting for age, smoking and outdoor activity.

    RESULTS: In Norway a large body size (silhouettes 6-9) compared to silhouette 3 increased the risk of MS, especially at age 25 (OR 2.21; 95% CI 1.09-4.46 for men and OR 1.43; 95% CI 0.90-2.27 for women). When comparing silhouette 9 to 1, we found a significant dose-response from age 10 until age 30 peaking at age 25 (sex-adjusted OR 2.83; 95% CI 1.68-4.78). The association was present for at least 15 years prior to disease onset. No significant associations were found in Italy.

    CONCLUSIONS: Obesity from childhood until young adulthood is a likely risk factor for MS with a seemingly stronger effect in Norway than in Italy.

  • 21.
    Westerlind, Helga
    et al.
    Karolinska Institute, Sweden.
    Boström, Inger
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet.
    Stawiarz, Leszek
    Karolinska Institute, Sweden.
    Landtblom, Anne-Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Medicinska specialistkliniken .
    Almqvist, Catarina
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Hillert, Jan
    Karolinska Institute, Sweden.
    New data identify an increasing sex ratio of multiple sclerosis in Sweden2014Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, nr 12, s. 1578-1583Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: An increasing women-to-men ratio in later birth cohorts of patients with multiple sclerosis (MS) has been observed in several populations and has been hypothesised to be due to one or several environmental factors of importance for disease aetiology. However, in a study based on data from the Swedish MS registry (SMSreg) this ratio was recently reported to be rather stable during the 20th century. Objective: The purpose of this study was to reinvestigate the women-to-men ratio in Sweden based on data from all available data sources, including deceased patients. Method: We combined data from the SMSreg with data from national patient registers. Results: In total we obtained information on 19,510 MS patients born 1931-1985, 13,321 women and 6189 men. The women-to-men ratio increased from 1.70 for patients born in the 1930s to 2.67 for patients born in the 1980s. When comparing the coverage of SMSreg to the full data set, a significantly higher proportion of women born 1931-1935 compared to men born in the same period were found in SMSreg, resulting in a sampling bias hiding the increasing sex ratio in the full material. Conclusion: The women-to-men ratio in MS has increased in Sweden during the 20th century similarly to observations in other western countries.

  • 22.
    Wickström, Anne
    et al.
    Umeå University, Sweden .
    Dahle, Charlotte
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Vrethem, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Svenningsson, Anders
    Umeå University, Sweden .
    Reduced sick leave in multiple sclerosis after one year of natalizumab treatment. A prospective ad hoc analysis of the TYNERGY trial2014Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, nr 8, s. 1095-1101Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    In a retrospective study, we have previously shown that work ability was improved after the initiation of natalizumab treatment in relapsing-remitting multiple sclerosis (RRMS). In another prospective trial (TYNERGY) the effect on MS-related fatigue was evaluated after 12 months of treatment with natalizumab. A comprehensive Capacity for Work Questionnaire (CWQ) was used to collect data regarding number of working hours and sickness absence. The predefined intention-to-treat analysis regarding work ability did not, however, show significant results.

    OBJECTIVES:

    The objective of this paper is to assess the amount of sick leave in RRMS before and after one year of natalizumab treatment and correlate it to fatigue and walking ability.

    METHODS:

    This is a post-hoc analysis of the complete data from the CWQ used in the TYNERGY trial.

    RESULTS:

    MS patients receiving sickness benefit before start of treatment reduced their sickness benefit by an absolute change of 33% after one year of natalizumab treatment. Younger age and improvement of walking ability correlated significantly with reduction of sick leave.

    CONCLUSIONS:

    This ad-hoc analysis of prospectively collected data supported our previous retrospective study and thus indicates a positive relationship between natalizumab treatment and improvement in work ability.

  • 23.
    Wickström, Anne
    et al.
    Umeå University, Sweden.
    Fagerström, Maria
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Rehabenheten.
    Wickström, Lucas
    Linköpings universitet, Institutionen för datavetenskap. Linköpings universitet, Tekniska fakulteten.
    Granasen, Gabriel
    Umeå University, Sweden.
    Dahle, Charlotte
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Vrethem, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Sundstrom, Peter
    Umeå University, Sweden.
    The impact of adjusted work conditions and disease-modifying drugs on work ability in multiple sclerosis2017Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 23, nr 8, s. 1137-1147Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Multiple sclerosis (MS) is a neurological disorder that causes significantly reduced ability to work, and the Expanded Disability Status Scale (EDSS) is one of the main predictors for reduced work ability. Objectives: To investigate how work requirements, flexible work conditions and disease-modifying drugs (DMDs) influence the work ability in relation to different EDSS grades in two MS populations. Methods: Work ability was studied in two MS populations: one in the southern and one in the northern part of Sweden, both demographically similar. In the latter population, more active work-promoting interventions have been practised and second-generation DMDs have been widely used from the onset of disease for several years. Results: The proportion of MS patients who participated in the workforce or studied was significantly higher in the northern compared with the southern population (pamp;lt;0.001). The employees in the northern population had significantly lower requirements, greater adapted work conditions and were able to work more hours per week. Higher EDSS was associated with lower reduction in number of worked hours per week in the northern population (p=0.042). Conclusion: Our data indicated that treatment strategy and adjusted work conditions have impact on work ability in MS.

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