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  • 1.
    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.

  • 2.
    Callander, Margarita
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet.
    Epidemiological and genetic studies of muliple sclerosis with focus on the Swedish county of Värmland2006Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The aim of this study was to perform detailed investigations of a presumed high-risk area, namely the county of Värmland, to see if previous results from our group indicating a high frequency of multiple sclerosis (MS) could be confirmed. We soon identified an aggregation of MS cases in the parish of Lysvik located in the north of Värmland and initiated epidemiological and genetical analyses of the population. We also extended our genetic research to include studies of a possible association between MS immunopathic trait and the MS susceptibility gene HLA-DR(2)15 type, but in another geographic area.

    The onset-adjusted prevalence of MS in Värmland was 170/105 (95% CI: 154-185) in December 2002, which is higher than prevalence previously reported from other Swedish areas. There was a great variation in MS frequency between communities in Värmland. We found a persistently high occurrence of MS in Torsby and Sunne communities. In the community of Årjäng MS frequency had increased substantially since the previous study performed by our group.

    Epidemiological analysis of a cluster of MS cases in Lysvik revealed 27 MS patients, of whom 23 were the descendants of a Finnish family originated from a common ancestor born in Savolaks in Finland in the 16th century and 18 had relatives with MS. Since this cluster was most likely to have a genetic basis (located in an area with a high inbreeding rate) the mode of MS inheritance was investigated. The linkage study using the genome-wide transmission disequilibrium test (TDT) provided several regions of interest, especially on chromosome 14q (14q24-31). The linkage peak on chromosome 17q was also confirmed by this study.

    The frequency of the HLA-DR(2)15 allele was higher in healthy siblings of MS patients without MS immunopathic trait (MSIT) than in siblings with the trait, which provides further support for the hypothesis that MSIT and MS are two independent, albeit, synergistic conditions.

    The prevalence study supports that Värmland County is a high-risk area. Furthermore, the aggregation of MS cases in Lysvik indicates a concentrated risk zone, possibly due to a combination of genetic, environmental and social risk factors. A widely and evenly spread environmental (i.e., infectious) agent together with cultural changes and industrialisation could possibly induce disease in subgroups of genetically more susceptible individuals. The evidence of linkage to chromosome 14 found in this study indicates that further genetic research is required.

    Delarbeten
    1. A cluster of multiple sclerosis cases in Lysvik in the Swedish county of Värmland
    Öppna denna publikation i ny flik eller fönster >>A cluster of multiple sclerosis cases in Lysvik in the Swedish county of Värmland
    2004 (Engelska)Ingår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 110, nr 1, s. 14-22Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Objectives – When surveying the county of Värmland in Sweden in order to determine the prevalence of multiple sclerosis (MS), we observed an aggregation of MS cases originating from the parish of Lysvik in the local region called Fryksdalen. Our intention was to analyse this cluster thoroughly, confirming the MS diagnosis and seeing if a hereditary or environmental background was plausible.

    Methods – The medical files were studied and the cases were classified by a neurologist according to Poser's criteria. Hereditary factors were analysed.

    Results – Sixteen living cases of MS were found, either living in the parish (n = 6) or born or raised there and had later moved to another place (n = 10). All patients had clinically definite MS. Eleven patients had relatives with MS, all of these being descendants of the Suhoinen family. Another two cases were Suhoinen descendants who did not have relatives with MS. Other common ancestors were also identified. Two cases were adopted. Eleven deceased MS patients from Lysvik were found, 10 of them had Suhoinen ancestry.

    Conclusion – We report a cluster of MS cases with a common ancestry indicating heredity for MS in 85% of the cases. Lysvik is a parish where Finnish immigration was pronounced in the 17th century and there has been inbreeding to a certain extent through marriage between cousins. Thus, we interpret this aggregation as possibly being genetically based, and neurogenetic studies are now being performed. However, as two of the cases were adopted environmental factors must also be considered.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-28710 (URN)10.1111/j.1600-0404.2004.00266.x (DOI)13879 (Lokalt ID)13879 (Arkivnummer)13879 (OAI)
    Tillgänglig från: 2009-10-09 Skapad: 2009-10-09 Senast uppdaterad: 2017-12-13Bibliografiskt granskad
    2. Genome-wide TDT analysis in a localized population with a high prevalence of multiple sclerosis indicates the importance of a region on chromosome 14q
    Öppna denna publikation i ny flik eller fönster >>Genome-wide TDT analysis in a localized population with a high prevalence of multiple sclerosis indicates the importance of a region on chromosome 14q
    Visa övriga...
    2003 (Engelska)Ingår i: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 4, nr 8, s. 559-563Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Epidemiological studies show that susceptibility to multiple sclerosis (MS) has a strong genetic component, but apart from the HLA gene complex, additional genetic factors have proven difficult to map in the general population. Thus, localized populations, where MS patients are assumed to be more closely related, may offer a better opportunity to identify shared chromosomal regions. We have performed a genome-wide scan with 834 microsatellite markers in a data set consisting of 54 MS patients and 114 healthy family members. A group of families from a small village were possible to track back to common ancestors living in the 17th century. We used single marker- and haplotype-based transmission disequilibrium test (TDT) analysis and nonparametric linkage analysis to analyze genotyping data. Regions on chromosomes 2q23–31, 6p24–21, 6q25–27, 14q24–32, 16p13–12 and 17q12–24 were found to be in transmission disequilibrium with MS. Strong transmission disequilibrium was detected in 14q24–32, where several dimarker haplotypes were in transmission disequilibrium in affected individuals. Several regions showed modest evidence for linkage, but linkage and TDT were both clearly positive only for 17q12–24. All patients and controls were also typed for HLA class II genes; however, no evidence for a gene–gene interaction was observed.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-27719 (URN)10.1038/sj.gene.6364024 (DOI)12457 (Lokalt ID)12457 (Arkivnummer)12457 (OAI)
    Tillgänglig från: 2009-10-08 Skapad: 2009-10-08 Senast uppdaterad: 2017-12-13Bibliografiskt granskad
    3. Multiple sclerosis immunopathic trait and HLA-DR(2)15 as independent risk factors in multiple sclerosis
    Öppna denna publikation i ny flik eller fönster >>Multiple sclerosis immunopathic trait and HLA-DR(2)15 as independent risk factors in multiple sclerosis
    Visa övriga...
    2007 (Engelska)Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 13, nr 4, s. 441-445Artikel i tidskrift (Refereegranskat) Published
    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.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-40847 (URN)10.1177/1352458506070264 (DOI)54299 (Lokalt ID)54299 (Arkivnummer)54299 (OAI)
    Tillgänglig från: 2009-10-10 Skapad: 2009-10-10 Senast uppdaterad: 2017-12-13Bibliografiskt granskad
    4. High prevalence of multiple sclerosis in the Swedish county of Värmland
    Öppna denna publikation i ny flik eller fönster >>High prevalence of multiple sclerosis in the Swedish county of Värmland
    2009 (Engelska)Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 15, nr 11, s. 1253-1262Artikel i tidskrift (Refereegranskat) Published
    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.

    Nyckelord
    epidemiological, risk, aetiological, genetics, environment
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-51888 (URN)10.1177/1352458509345909 (DOI)
    Tillgänglig från: 2009-11-23 Skapad: 2009-11-23 Senast uppdaterad: 2017-12-12Bibliografiskt granskad
  • 3.
    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.

  • 4.
    Callander, Margarita
    et al.
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Neurologi. Linköpings universitet, Hälsouniversitetet.
    Landtblom, Anne-Marie
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Neurologi. Linköpings universitet, Hälsouniversitetet.
    A cluster of multiple sclerosis cases in Lysvik in the Swedish county of Värmland2004Ingår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 110, nr 1, s. 14-22Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives – When surveying the county of Värmland in Sweden in order to determine the prevalence of multiple sclerosis (MS), we observed an aggregation of MS cases originating from the parish of Lysvik in the local region called Fryksdalen. Our intention was to analyse this cluster thoroughly, confirming the MS diagnosis and seeing if a hereditary or environmental background was plausible.

    Methods – The medical files were studied and the cases were classified by a neurologist according to Poser's criteria. Hereditary factors were analysed.

    Results – Sixteen living cases of MS were found, either living in the parish (n = 6) or born or raised there and had later moved to another place (n = 10). All patients had clinically definite MS. Eleven patients had relatives with MS, all of these being descendants of the Suhoinen family. Another two cases were Suhoinen descendants who did not have relatives with MS. Other common ancestors were also identified. Two cases were adopted. Eleven deceased MS patients from Lysvik were found, 10 of them had Suhoinen ancestry.

    Conclusion – We report a cluster of MS cases with a common ancestry indicating heredity for MS in 85% of the cases. Lysvik is a parish where Finnish immigration was pronounced in the 17th century and there has been inbreeding to a certain extent through marriage between cousins. Thus, we interpret this aggregation as possibly being genetically based, and neurogenetic studies are now being performed. However, as two of the cases were adopted environmental factors must also be considered.

  • 5.
    Giedraitis, V.
    et al.
    Division of Neurology, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden.
    Modin, H.
    Division of Neurology, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden.
    Callander, Margarita
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Neurologi. Linköpings universitet, Hälsouniversitetet.
    Landtblom, Anne-Marie
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Neurologi. Linköpings universitet, Hälsouniversitetet.
    Fossdal, R.
    deCODE Genetics, Reykjavik, Iceland.
    Stefansson, K.
    deCODE Genetics, Reykjavik, Iceland.
    Hillert, J.
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Neurologi. Linköpings universitet, Hälsouniversitetet.
    Gulcher, J.
    deCODE Genetics, Reykjavik, Iceland.
    Genome-wide TDT analysis in a localized population with a high prevalence of multiple sclerosis indicates the importance of a region on chromosome 14q2003Ingår i: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 4, nr 8, s. 559-563Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Epidemiological studies show that susceptibility to multiple sclerosis (MS) has a strong genetic component, but apart from the HLA gene complex, additional genetic factors have proven difficult to map in the general population. Thus, localized populations, where MS patients are assumed to be more closely related, may offer a better opportunity to identify shared chromosomal regions. We have performed a genome-wide scan with 834 microsatellite markers in a data set consisting of 54 MS patients and 114 healthy family members. A group of families from a small village were possible to track back to common ancestors living in the 17th century. We used single marker- and haplotype-based transmission disequilibrium test (TDT) analysis and nonparametric linkage analysis to analyze genotyping data. Regions on chromosomes 2q23–31, 6p24–21, 6q25–27, 14q24–32, 16p13–12 and 17q12–24 were found to be in transmission disequilibrium with MS. Strong transmission disequilibrium was detected in 14q24–32, where several dimarker haplotypes were in transmission disequilibrium in affected individuals. Several regions showed modest evidence for linkage, but linkage and TDT were both clearly positive only for 17q12–24. All patients and controls were also typed for HLA class II genes; however, no evidence for a gene–gene interaction was observed.

  • 6.
    Landtblom, Anne-Marie
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Neurologi. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Flensner, Gullvi
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Omvårdnad.
    Callander, Margarita
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Neurologi. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Stawiarz, Leszek
    Svenska MS-registret lyfter fram ett viktigt kliniskt problem. Fysisk och psykisk uttröttbarhet ett huvudsymtom vid multipel skleros2004Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 101, s. 3456-3457Artikel i tidskrift (Övrigt vetenskapligt)
  • 7.
    Lundgren, Fredrik
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Kärlkirurgi. Östergötlands Läns Landsting, Hjärtcentrum, Thorax-kärlkliniken.
    Callander, Margarita
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Forssell, Claes
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Kärlkirurgi. Östergötlands Läns Landsting, Hjärtcentrum, Thorax-kärlkliniken.
    Rydén, Bengt-Olof
    Stahre, Bengt-Olof
    Teoretisk modell för utveckling av AAA-operationer och ruturdöd efter införande av 65-årsscreening för män2002Ingår i: Svensk kirurgi,2002, 2002, s. 160-160Konferensbidrag (Refereegranskat)
  • 8.
    Valladares, Carlos
    et al.
    Kardiologiska kliniken Hjärtcentrum.
    Broqvist, Mats
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Kardiologi. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Nylander, Eva
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk fysiologi. Östergötlands Läns Landsting, Hjärtcentrum, Fysiologiska kliniken.
    Callander, Margarita
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Neurologi. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Var det paradoxal embolism? Cerebellär infarkt, öppetstående foramen ovale och APC-resistens - en kontroversiell kombination och terapeutisk utmaning2006Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 103, s. 845-848Artikel i tidskrift (Övrigt vetenskapligt)
  • 9.
    Vigren, Patrik
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Neurokirurgiska kliniken US.
    Ström, Jakob
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet.
    Petrini, Pia
    Karolinska University Hospital, Sweden .
    Callander, Margarita
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Theodorsson, Annette
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Neurokirurgiska kliniken US.
    Treatment of spontaneous intracerebral haemorrhage in Glanzmanns thrombasthenia2012Ingår i: Haemophilia, ISSN 1351-8216, E-ISSN 1365-2516, Vol. 18, nr 5, s. e381-e383Artikel i tidskrift (Övrigt vetenskapligt)
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