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1.	Ahlgren, Cecilia, 1946, et al. (författare) A population-based case-control study on viral infections and vaccinations and subsequent multiple sclerosis risk. 2009 Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 1573-7284 .- 0393-2990. ; 24:9, s. 541-52 Tidskriftsartikel (refereegranskat)abstract 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.
2.	Ahlgren, Cecilia, 1946, et al. (författare) High risk of MS in Iranian immigrants in Gothenburg, Sweden. 2010 Ingår i: Multiple sclerosis journal. - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 16:9, s. 1079-1082 Tidskriftsartikel (refereegranskat)abstract 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.
3.	Ahlgren, Cecilia, 1946, et al. (författare) Multiple sclerosis incidence in the era of measles-mumps-rubella mass vaccinations. 2009 Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 119:5, s. 313-20 Tidskriftsartikel (refereegranskat)abstract 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. OBJECTIVES: To examine whether the vaccination induced reduction in these infections influences the MS incidence. In addition, the public health aspect justified an early evaluation of beneficial as well as harmful effects of mass vaccinations. MATERIALS AND METHODS: From an incidence material of 534 MS patients, born 1959-1990, we selected one unvaccinated cohort and four cohorts, each corresponding to a vaccination program (MS patients = 251). RESULTS: With the ability to detect a decrease by 30-35%, and an increase by 37-48% in the MS incidence in the first three cohorts, we found no vaccination related MS incidence changes. The background MS incidence showed a significant gradual age dependent increase. CONCLUSIONS: While the present follow-up provided limited power in the last cohort, there is no evidence as yet that the radical decline in three viral infections influenced the MS incidence. However, the increasing background MS incidence of unknown cause may have concealed a reduction in MS risk associated with mass vaccinations.
4.	Ahlgren, Cecilia, 1946, et al. (författare) No major birth order effect on the risk of multiple sclerosis 2005 Ingår i: Neuroepidemiology. ; 24, s. 38-41 Tidskriftsartikel (refereegranskat)abstract Abstract In the present study, we found no association between multiple sclerosis (MS; definite and probable, n = 211) and birth order (p = 0.1411). The observed number of first-born patients did not differ significantly from the expected number (p = 0.0871). While there was a significantly high birth order (n = 258, p = 0.0381) and a marginally significant low number of first-borns (p = 0.0475) when possible MS cases were included, an artefact due to the population structure may have accentuated this result. In comparison with the control birth cohort, there was no significant association with birth order (p = 0.0742) or the proportion of first-borns (p = 0.220) in a subgroup from the MS incidence cohort born between 1915 and 1929 (n = 158). Birth order had no major impact on the risk of subsequent MS in this study. Copyright © 2005 S. Karger AG, Basel
5.	Ahlgren, Cecilia, 1946, et al. (författare) 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. 2011 Ingår i: Journal of neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 235:1-2, s. 98-103 Tidskriftsartikel (refereegranskat)abstract 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.
6.	Andersen, Oluf, 1941 (författare) Conclusion: National incidence and risk factor assessments may become a basis for the evaluation of prevention trials - prospects from the Third Nordic MS Symposium 2015 Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314. ; 132:S199, s. 71-75 Forskningsöversikt (refereegranskat)abstract This symposium started with an overview of recent incidence and prevalence data from the Scandinavian national registers and continued with a critical analysis of several alleged risk factors for MS. These risk factors are constantly changing and therefore might explain current incidence changes. In addition, they may be the subject of preventive measures.
7.	Andersen, Oluf, 1941 (författare) Current immunotherapy in relapsing-remitting MS reduces the risk of transition to secondary progression. A 10-year study using virtual placebo technique based on hazard functions. Oral presentation, EFNS, Madrid 2008. 2008 Ingår i: Europ J Neurol. ; 15:Suppl 3:26 Konferensbidrag (refereegranskat)
8.	Andersen, Oluf, 1941, et al. (författare) Diffusion tensor imaging in multiple sclerosis at different final outcomes 2018 Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 137:2, s. 165-173 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES:Methods to evaluate the relative contributions of demyelination vs axonal degeneration over the long-term course of MS are urgently needed. We used magnetic resonance diffusion tensor imaging (DTI) to estimate degrees of demyelination and axonal degeneration in the corpus callosum (CC) in cases of MS with different final outcomes.MATERIALS AND METHODS:We determined DTI measures mean diffusivity (MD), fractional anisotropy (FA), and axial (AD) and radial (RD) diffusivities in the CC of 31 MS patients, of whom 13 presented a secondary progressive course, 11 a non-progressive course, and seven a monophasic course. The study participants were survivors from an incidence cohort of 254 attack-onset MS patients with 50 years of longitudinal follow-up. As reference, we included five healthy individuals without significant morbidity.RESULTS:In patients with secondary progression, compared to all other groups, the corpus callosum showed increased RD and reduced FA, but no change in AD. None of the parameters exhibited differences among non-progressive and monophasic course groups and controls.CONCLUSION:Increased RD was observed in secondary progressive MS, indicating significant myelin loss. Normal RD values observed in the clinically isolated syndrome and non-progressive groups confirm their benign nature. AD was not a characterizing parameter for long-term outcome. Demyelination revealed by increased RD is a distinguishing trait for secondary progression.
9.	Andersen, Oluf, 1941 (författare) Disease mechanisms in MS: Phases of disease improvement unrelated to relapses. 2012 Ingår i: Nature reviews. Neurology. - : Springer Science and Business Media LLC. - 1759-4766 .- 1759-4758. ; 8:11, s. 596-8 Forskningsöversikt (refereegranskat)abstract Natural history of multiple sclerosis includes phases of relapse, remission and insidious progression. New data show that sustained improvements in disease, defined by reductions in EDSS scores, occur independent of relapses almost half as frequently as disease worsening. This finding might facilitate research into the biological processes involved in disease improvement.
10.	Andersen, Oluf, 1941 (författare) From the Gothenburg cohort to the Swedish multiple sclerosis registry 2012 Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314. ; 126, s. 13-19 Tidskriftsartikel (refereegranskat)abstract An overview of prevalence and incidence studies performed in Swedish centres is provided, showing improving coverage and methodology, notably the development in Gothenburg of the representative incidence cohort design. A common database for major Swedish centres was established in 1995, implementing the terminology of predictors from the Gothenburg cohort. By 2001, these databases were merged into the web-based national multiple sclerosis (MS) registry, which has had an ever-increasing coverage, although with still moderate data density. The registry now contains records on 13,000 Swedish patients with MS. It has the status of a national quality registry and exerts nation-wide pharmacological surveillance. In addition, it has been, and is being, used in nearly 100 scientific studies, including large epidemiological and genetic projects.
11.	Andersen, Oluf, 1941 (författare) MS and infections - Abandoned and surviving hypotheses 2017 Ingår i: Acta Neurologica Scandinavica, Supplementum. - : Hindawi Limited. - 0065-1427 .- 0001-6314. ; 136:S201, s. 4-9 Forskningsöversikt (refereegranskat)abstract In this introduction, we follow the ups and downs of infections in MS pathogenesis. Our arguments focus on specific agents and events, not referring to general MS epidemiology. The historical approach continues on to contemporary data and a critical analysis.
12.	Andersen, Oluf, 1941, et al. (författare) Multicentre, randomised, double blind, placebo controlled, phase III study of weekly, low dose, subcutaneous interferon beta-1a in secondary progressive multiple sclerosis 2004 Ingår i: JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY. - : BMJ. - 0022-3050 .- 1468-330X. ; 75:5, s. 706-710 Tidskriftsartikel (refereegranskat)
13.	Andersen, Oluf, 1941, et al. (författare) Multipel skleros. Fagius J (ed) 2007 Bok (övrigt vetenskapligt/konstnärligt)
14.	Andersen, Oluf, 1941 (författare) Nordic MS Epidemiology. Introduction. 2015 Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314. ; 132:S199, s. 1-3 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
15.	Andersen, Oluf, 1941 (författare) Predicting a window of therapeutic opportunity in multiple sclerosis. 2010 Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 133:Pt 7, s. 1863-5 Forskningsöversikt (refereegranskat)
16.	Andersen, Oluf, 1941, et al. (författare) Predictive MS risk factors and axonal disintegration 2020 Ingår i: Neurology. - 0028-3878. ; 94:18, s. 771-772 Tidskriftsartikel (refereegranskat)abstract EDITORIAL. The important take-home message of the study by Cortese et al. is that the serum NfL seems to be useful not only for assessing the current status of patients but also as a long-term outcome. Related article; Cortese et al.: Vitamin D, smoking, EBV, and long-term cognitive performance in MS: 11-year follow-up of BENEFIT. Neurology 2020;94:781.
17.	Andersen, Oluf, 1941 (författare) The natural history of multiple sclerosis. 2008 Ingår i: Multiple Sclerosis. A Comprehensive Text. Raine C, MacFarland H, Hohlfeld R. (eds.). - Amsterdam : Elsevier. - 9780702028113 Bokkapitel (övrigt vetenskapligt/konstnärligt)
18.	Andersen, Oluf, 1941, et al. (författare) Treatment Options for Epstein-Barr Virus-Related Disorders of the Central Nervous System. 2023 Ingår i: Infection and drug resistance. - 1178-6973. ; 16, s. 4599-4620 Forskningsöversikt (refereegranskat)abstract Epstein-Barr virus (EBV), a causative agent for several types of lymphomas and mucosal cancers, is a human lymphotropic herpesvirus with the capacity to establish lifelong latent infection. More than 90% of the human population worldwide is infected. The primary infection is usually asymptomatic in childhood, whereas infectious mononucleosis (IM) is common when the infection occurs in adolescence. Primary EBV infection, with or without IM, or reactivation of latent infection in immunocompromised individuals have been associated with a wide range of neurologic conditions, such as encephalitis, meningitis, acute disseminated encephalomyelitis, and cerebellitis. EBV is also involved in malignant lymphomas in the brain. An increasing number of reports on EBV-related disorders of the central nervous system (CNS) including the convincing association with multiple sclerosis (MS) have put in focus EBV-related conditions beyond its established link to malignancies. In this review, we present the clinical manifestations of EBV-related CNS-disorders, put them in the context of known EBV biology and focus on available treatment options and future therapeutic approaches.
19.	Andersen, Oluf, 1941 (författare) Tänk på risken för pseudoskov vid högfebril covid-19 hos MS-sjuka 2020 Ingår i: Läkartidningen. - 0023-7205. ; 117:25-27 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Syftet med detta bidrag är att peka på risken för symtomgivande feberutlösta pseudoskov vid högfebril covid-19-infektion hos MS-sjuka.
20.	Axelsson, Markus, 1975, et al. (författare) Neurofilament light protein levels in cerebrospinal fluid predict long-term disability of Guillain-Barré syndrome: A pilot study. 2018 Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 138:2, s. 143-150 Tidskriftsartikel (refereegranskat)abstract Although the recovery from Guillain-Barré syndrome (GBS) is good in most patients, some develop permanent severe disability or even die. Early predictors would increase the likelihood to identify patients at risk for poor outcome at the acute stage, allowing them intensified therapeutic intervention.Eighteen patients with a history of GBS 9-17years ago were reassessed with scoring of neurological disability and quality of life assessment (QoL). Their previous diagnostic work-up included clinical examination with scoring of disability, neurophysiological investigation, a battery of serology tests for infections, and cerebrospinal fluid (CSF) examination. Aliquots of CSF were frozen, stored for 20-28years, and analyzed by ELISA for determination of neurofilament light protein (NFL) and glial fibrillary acidic protein (GFAP).Patients with poor outcome (n=3) had significantly higher NFL and GFAP levels at GBS nadir than those with good outcome (n=15, P<.01 and P<.05, respectively). High NFL correlated with more prominent disability and worse QoL at long-term follow-up (r=.694, P<.001, and SF 36 dimension physical component summary (PCS) (r =-.65, P<.05), respectively, whereas GFAP did not correlate with clinical outcome or QoL.High NFL in CSF at the acute stage of GBS seems to predict long-term outcome and might, together with neurophysiological and clinical measures, be useful in treatment decisions and clinical care of GBS.
21.	Beiske, A G, et al. (författare) Health-related quality of life in secondary progressive multiple sclerosis. 2007 Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 13:3, s. 386-92 Tidskriftsartikel (refereegranskat)abstract Common disability scales in multiple sclerosis (MS) are often weighted towards physical disability. Non-motor symptoms such as depression, fatigue and pain substantially influence wellbeing in MS. Health-related quality of life (HRQoL) measures the broader impact of MS and might indicate less obvious disease burdens. We analysed HRQoL, using the Nottingham Health Profile Part I (NHP-I), among 345 secondary progressive MS (SPMS) patients participating in a randomized trial of interferon-beta1a (IFN-beta1a), 22 mug subcutaneously weekly, or matching placebo. The results did not reveal any beneficial effect of IFN-beta1a in any outcome measure. NHP-I sub- and sum scores were compared for 217 population controls and correlated with demographic and clinical disease variables. SPMS patients had lower NHP-I sum and all subscores than the controls. Patients experiencing disease progression reported worse NHP-I sum scores. Increased fatigue, Expanded Disability Status Scale (EDSS) and Arm Index scores were independently associated with reduction in several NHP-I subscores. SPMS patients had significantly lower HRQoL than controls and physical disability (EDSS and Arm Index), disease progression and fatigue strongly influenced this. MS.
22.	Biström, Martin, et al. (författare) Epstein-Barr virus infection after adolescence and Human herpesvirus 6A as risk factors for multiple sclerosis 2021 Ingår i: European Journal of Neurology. - : Blackwell Publishing. - 1351-5101 .- 1468-1331. ; 28:2, s. 579-586 Tidskriftsartikel (refereegranskat)abstract Background and purpose: Infections with human herpesvirus 6A (HHV-6A) and Epstein–Barr virus (EBV) have been linked to multiple sclerosis (MS) development. For EBV, late infection has been proposed as a risk factor, but serological support is lacking. The objective of this study was to investigate how age affects the EBV and HHV-6A associated risks of developing MS.Methods: In this nested case–control study, Swedish biobanks were accessed to find pre-symptomatically collected blood samples from 670 individuals who later developed relapsing MS and 670 matched controls. A bead-based multiplex assay was used to determine serological response against EBV and HHV-6A. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals.Results: Seropositivity against EBV exhibited a pattern where associations switched from a decreased risk of developing MS in the group below 20 years of age to an increased risk amongst individuals aged 20–29 and 30–39 years (p for trend 0.020). The age of transition was estimated to be 18.8 years. In contrast, HHV-6A was associated with increased MS risk in all age groups (total cohort odds ratio 2.1, 95% confidence interval 1.6–2.7).Conclusions: This study suggests EBV infection after adolescence and age independent HHV-6A infection as risk factors for MS.
23.	Biström, Martin, et al. (författare) High serum concentration of vitamin D may protect against multiple sclerosis 2019 Ingår i: Multiple Sclerosis Journal, Experimental, Translational and Clinical. - : Sage Publications. - 2055-2173. ; 5:4 Tidskriftsartikel (refereegranskat)abstract Background: High 25-hydroxyvitamin D concentrations have been associated with a reduced risk of multiple sclerosis, with indications of a stronger effect among young individuals.Objective: Investigate the 25-hydroxyvitamin D association with multiple sclerosis and test if this association is age dependent.Methods: Prospectively drawn blood samples from individuals later developing relapsing-remitting multiple sclerosis and controls matched for biobank, sex, age and date of sampling, were analysed with liquid chromatography tandem mass spectrometry.Results: High levels of 25-hydroxyvitamin D (top quintile) were associated with a reduced multiple sclerosis risk (odds ratio 0.68, 95% confidence interval 0.50-0.93).Conclusion: These findings further support a role for vitamin D in MS aetiology.
24.	Biström, Martin, 1982-, et al. (författare) Leptin levels are associated with multiple sclerosis risk 2021 Ingår i: Multiple Sclerosis Journal. - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 27:1, s. 19-27 Tidskriftsartikel (refereegranskat)abstract Background: Obesity early in life has been linked to increased risk of developing multiple sclerosis (MS). Leptin and insulin are both associated with obesity, making them suitable candidates for investigating this connection. Objective: To determine if leptin and insulin are risk factors for relapsing-remitting multiple sclerosis (RRMS). Methods: In this nested case-control study using blood samples from Swedish biobanks, we compared concentrations of leptin and insulin in 649 individuals who later developed RRMS with 649 controls matched for biobank, sex, age and date of sampling. Only pre-symptomatically drawn samples from individuals below the age of 40 years were included. Conditional logistic regression was performed on z-scored values to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Results: A 1-unit leptin z-score increase was associated with increased risk of MS in individuals younger than 20 years (OR = 1.4, 95% CI = 1.1-1.9) and in all men (OR = 1.4, 95% CI = 1.0-2.0). In contrast, for women aged 30-39 years, there was a lower risk of MS with increased leptin levels (OR = 0.74, 95% CI = 0.54-1.0) when adjusting for insulin levels. Conclusion: We show that the pro-inflammatory adipokine leptin is a risk factor for MS among young individuals.
25.	Callander, Margarita, et al. (författare) Multiple sclerosis immunopathic trait and HLA-DR(2)15 as independent risk factors in multiple sclerosis 2007 Ingår i: Multiple Sclerosis. ; 13:4, s. 441-445 Tidskriftsartikel (refereegranskat)
26.	Craggs, Lucinda, et al. (författare) Quantitative vascular pathology and phenotyping familial and sporadic cerebral small vessel diseases 2013 Ingår i: Brain Pathology. - : Wiley. - 1015-6305 .- 1750-3639. ; 23:5, s. 547-557 Tidskriftsartikel (refereegranskat)abstract We quantified vascular changes in the frontal lobe and basal ganglia of four inherited small vessel diseases (SVDs) including cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL), hereditary multi-infarct dementia of Swedish type (Swedish hMID), and hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS). Vascular pathology was most severe in CADASIL, and varied with marginally greater severity in the basal ganglia compared to the frontal lobe. The overall sclerotic index values in frontal lobe were in the order CADASIL≥HERNS>PADMAL>Swedish hMID>sporadic SVD, and in basal ganglia CADASIL>HERNS>Swedish hMID>PADMAL> sporadic SVD. The subcortical white matter was almost always more affected than any gray matter. We observed glucose transporter-1 (GLUT-1) protein immunoreactivities were most affected in the white matter indicating capillary degeneration whereas collagen IV (COL4) immunostaining was increased in PADMAL cases in all regions and tissue types. Overall, GLUT-1:COL4 ratios were higher in the basal ganglia indicating modifications in capillary density compared to the frontal lobe. Our study shows that the extent of microvascular degeneration varies in these genetic disorders exhibiting common end-stage pathologies but is the most aggressive in CADASIL.
27.	Darin, Niklas, 1964, et al. (författare) 3-methylcrotonyl-CoA carboxylase deficiency and severe multiple sclerosis. 2007 Ingår i: Pediatric neurology. - : Elsevier BV. - 0887-8994. ; 36:2, s. 132-4 Tidskriftsartikel (refereegranskat)abstract This report describes a female with isolated 3-methylcrotonyl-CoA carboxylase deficiency. She had a mild Reye-like episode, loss of scalp hair, psychomotor retardation, and an attention-deficit hyperactivity disorder. The diagnosis was made at 13 years of age when she developed relapsing remitting multiple sclerosis with a malignant course. Treatment with steroids had initially a good therapeutic effect on the relapses. The response to interferon beta-1a treatment was poor. On mitoxantrone treatment there was a considerable neurologic recovery.
28.	Datta, P., et al. (författare) A follow-up study of Nordic multiple sclerosis candidate gene regions 2007 Ingår i: MULTIPLE SCLEROSIS. - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 13:5, s. 584-589 Tidskriftsartikel (refereegranskat)abstract In this study, the results from three Nordic linkage disequilibrium screens in multiple sclerosis (MS) were investigated, in a new sample set of 314 Nordic MS trios from Denmark, Norway, Sweden and Iceland. Among 30 non-HLA and two HLA microsatellite markers individually genotyped, eight markers displayed distorted transmission with uncorrected P-value <0.05, ranked in this order: D6S2443 (6p21.32, HLA class II) (P corrected =0.01), D2S2201 (2p24), D19S552 (19q13), D3S3584 (3q21), D17S975 (17q11), D1S2627 (1p22), D6S273 (6p21.33, HLA class III) and D12S1051 (12q23). These non-HLA regions need further investigation as possible MS candidate gene regions in our population. Multiple Sclerosis 2007; 13: 584-589. http://msj.sagepub.com
29.	Ekström, Anita, et al. (författare) Vård av människor med avancerad MS. 2007 Ingår i: Metodboken. Sundström P, Myr Å, Vrethem M, Walentin F (ed).. - Stockholm : Svenska MS-sällskapet. Bokkapitel (övrigt vetenskapligt/konstnärligt)
30.	Engdahl, Elin, et al. (författare) Increased Serological Response Against Human Herpesvirus 6A Is Associated With Risk for Multiple Sclerosis 2019 Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 10 Tidskriftsartikel (refereegranskat)abstract Human herpesvirus (HHV)-6A or HHV-6B involvement in multiple sclerosis (MS) etiology has remained controversial mainly due to the lack of serological methods that can distinguish the two viruses. A novel multiplex serological assay measuring IgG reactivity against the immediate-early protein 1 from HHV-6A (IE1A) and HHV-6B (IE1B) was used in a MS cohort (8,742 persons with MS and 7,215 matched controls), and a pre-MS cohort (478 individuals and 476 matched controls) to investigate this further. The IgG response against IE1A was positively associated with MS (OR = 1.55, p = 9 × 10-22), and increased risk of future MS (OR = 2.22, p = 2 × 10-5). An interaction was observed between IE1A and Epstein-Barr virus (EBV) antibody responses for MS risk (attributable proportion = 0.24, p = 6 × 10-6). In contrast, the IgG response against IE1B was negatively associated with MS (OR = 0.74, p = 6 × 10-11). The association did not differ between MS subtypes or vary with severity of disease. The genetic control of HHV-6A/B antibody responses were located to the Human Leukocyte Antigen (HLA) region and the strongest association for IE1A was the DRB113:01-DQA101:03-DQB106:03 haplotype while the main association for IE1B was DRB113:02-DQA101:02-DQB106:04. In conclusion a role for HHV-6A in MS etiology is supported by an increased serological response against HHV-6A IE1 protein, an interaction with EBV, and an association to HLA genes.
31.	Granberg, Tobias, et al. (författare) Hereditary diffuse leukoencephalopathy with spheroids - a volumetric and radiological comparison with multiple sclerosis patients and healthy controls. 2016 Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 23:4, s. 817-822 Tidskriftsartikel (refereegranskat)abstract Background and purpose Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal dominant disorder caused by colony-stimulating factor 1 receptor (CSF1R) gene mutations, resulting in demyelination and axonal degeneration with spheroids. The clinical expression is variable, including behavioral changes, cognitive impairment, motor symptoms and parkinsonism. Magnetic resonance imaging (MRI) reveals white matter (WM) changes and atrophy. The indistinct phenotype has led to misdiagnoses. This study's aim was to compare brain volumetry and radiological ratings in HDLS with multiple sclerosis (MS) patients and controls. Methods Five HDLS patients with c.2562T>A p.Asn854Lys CSF1R mutation, five age- and gender-matched MS patients and five healthy controls were cross-sectionally studied. All patients were examined neurologically. HDLS patients underwent Mini-Mental State Examination (MMSE). Brain MRI scans were analyzed volumetrically with FreeSurfer and Lesion Segmentation Toolbox and neuroradiologically with the brain MRI scoring system for HDLS. Results Patients with HDLS had lower brain, grey matter and WM fractions (66.3%; 37.9%; 27.6%) compared with controls (78.5%, P = 0.008; 44.4%, P = 0.008; 32.0%, P = 0.008), but not compared with MS patients (65.7%, P = 0.7; 36.8%, P = 0.4; 27.3%, P = 0.7). Cerebellar WM changes and atrophy were not seen in the HDLS group. The HDLS lesion volume fraction correlated with MMSE scores (r = −0.90, P = 0.04). Conclusions Brain volume fractions in HDLS were lower than in controls and similar to those seen in MS. The cerebellum was relatively spared in HDLS, which may help in differentiating HDLS WM changes from MS. The strong relationship of HDLS lesions with MMSE scores indicates that accumulating WM pathology in HDLS is associated with cognitive decline.
32.	Grut, Viktor, et al. (författare) Cytomegalovirus seropositivity is associated with reduced risk of multiple sclerosis : a presymptomatic case-control study 2021 Ingår i: European Journal of Neurology. - : Blackwell Publishing. - 1351-5101 .- 1468-1331. ; 28:9, s. 3072-3079 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Epstein-Barr virus (EBV) and Human herpesvirus 6A (HHV-6A) are associated with increased risk of multiple sclerosis (MS). Conversely, infection with Cytomegalovirus (CMV) has been suggested to reduce the risk of MS but supporting data from presymptomatic studies are lacking. Here, we sought to increase the understanding of CMV in MS aetiology.METHODS: We performed a nested case-control study with presymptomatically collected blood samples identified through cross-linkage of MS registries and Swedish biobanks. Serological antibody response against CMV, EBV and HHV-6A was determined using a bead-based multiplex assay. Odds ratio (OR) with 95 % confidence intervals (CI) for CMV seropositivity as risk factor for MS was calculated by conditional logistic regression and adjusted for EBV and HHV-6A seropositivity. Potential interactions on the additive scale were analysed by calculating attributable proportion due to interaction (AP).RESULTS: Serum samples from 670 pairs of matched cases and controls were included. CMV seropositivity was associated with a reduced risk for MS (OR = 0.70, 95% CI 0.56-0.88, p = 0.003). Statistical interactions on the additive scale were observed between seronegativity for CMV and seropositivity against HHV-6A (AP 0.34, 95% CI 0.06-0.61) and EBV antigen EBNA-1 (amino acid 385-420) at age 20-39 years (AP 0.37, 95% CI 0.09-0.65).CONCLUSIONS: CMV seropositivity is associated with a decreased risk for MS. The protective role for CMV infection in MS aetiology is further supported by the interactions between CMV seronegativity and EBV and HHV-6A seropositivity.
33.	Grut, Viktor, et al. (författare) Free vitamin D3 index and vitamin D-binding protein in multiple sclerosis : A presymptomatic case-control study 2022 Ingår i: European Journal of Neurology. - : John Wiley & Sons. - 1351-5101 .- 1468-1331. ; 29:8, s. 2335-2342 Tidskriftsartikel (refereegranskat)abstract BACKGROUND AND PURPOSE: High levels of 25-hydroxyvitamin D3 (25[OH]D3 ) are associated with a lower risk for multiple sclerosis (MS). The bioavailability of 25(OH)D3 is regulated by its main plasma carrier, vitamin D-binding protein (DBP). Free 25(OH)D3 can be estimated by also measuring DBP concentration. In addition, DBP has immunomodulatory functions that may independently affect MS pathogenesis. No previous studies have assessed free 25(OH)D3 or DBP in presymptomatically collected samples. This study was undertaken to assess free 25(OH)D3 and DBP as risk factors for MS.METHODS: A nested case-control study was performed with presymptomatic serum samples identified through cross-linkage of MS registries and Swedish biobanks. Concentration of 25(OH)D3 was measured with liquid chromatography and DBP levels with sandwich immunoassay. Free 25(OH)D3 was approximated as free vitamin D3 index: (25[OH]D3 /DBP) × 103 . MS risk was analyzed by conditional logistic regression, calculating odds ratios (ORs) with 95% confidence intervals (CIs).RESULTS: Serum samples from 660 pairs of matched cases and controls were included. At <20 years of age, high levels of free vitamin D3 index were associated with a lower risk of MS (highest vs. lowest quintile: OR = 0.37, 95% CI = 0.15-0.91, p for trend across quintiles = 0.04). At age 30-39 years, high levels of DBP were associated with a lower MS risk (highest vs. lowest quintile: OR = 0.36, 95% CI = 0.15-0.85, p for trend = 0.02).CONCLUSIONS: These findings support the hypothesis that high levels of free 25(OH)D3 at a young age reduce the risk of MS later in life. They also implicate a role for DBP in MS etiology.
34.	Grut, Viktor, et al. (författare) Systemic inflammation and risk of multiple sclerosis – A presymptomatic case-control study 2022 Ingår i: Multiple Sclerosis Journal - Experimental, Translational and Clinical. - : SAGE Publications. - 2055-2173. ; 8:4 Tidskriftsartikel (refereegranskat)abstract Background: C-reactive protein (CRP) is a marker of systemic inflammation. Increased levels of CRP in young persons have been suggested to decrease the risk of multiple sclerosis (MS). Objectives: To assess CRP as a risk factor for MS. Methods: Levels of CRP were measured with a high-sensitive immunoassay in biobank samples from 837 individuals who later developed MS and 984 matched controls. The risk of developing MS was analysed by conditional logistic regression on z-scored CRP values. Results: Levels of CRP were not associated with MS risk. Conclusions: We found no association between CRP levels and risk of MS development.
35.	Görander, Staffan, 1952, et al. (författare) Multiphasic encephalomyelitis in a patient with recurrent herpes simplex type 2 meningitis. 2006 Ingår i: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 38:10, s. 942-5 Tidskriftsartikel (refereegranskat)abstract We here describe a patient with a history of recurrent HSV-2 meningitis who had been free from symptoms for almost 20 y when he developed an acute encephalomyelitis. The clinical course laboratory and radiological findings support an acute multiphasic disseminated encephalomyelitis induced by a recurrent HSV-2 infection.
36.	Haghighi, Sara, et al. (författare) A linkage study in two families with multiple sclerosis and healthy members with oligoclonal CSF immunopathy 2006 Ingår i: Multiple Sclerosis. ; 12:6, s. 723-730 Tidskriftsartikel (refereegranskat)
37.	Haghighi, Sara, et al. (författare) Cerebrospinal fluid markers in MS patients and their healthy siblings 2004 Ingår i: ACTA NEUROLOGICA SCANDINAVICA. - 0001-6314. ; 109:2, s. 97-99 Tidskriftsartikel (refereegranskat)
38.	Haghighi, Sara, et al. (författare) Incidence of CSF abnormalities in siblings of multiple sclerosis patients and unrelated controls. 2000 Ingår i: Journal of neurology. - 0340-5354 .- 1432-1459. ; 247:8, s. 616-22 Tidskriftsartikel (refereegranskat)abstract We found that 19% (9/47) of healthy siblings of patients with clinically definite multiple sclerosis had an intrathecal immunological reaction with two or more 2 CSF-enriched oligoclonal bands (OCBs), in contrast to (4%) (2/50) unrelated healthy controls. Furthermore, in this group of nine healthy sibs the measles CSF IgG antibody titers were higher than that of the other sibs and that of controls. There were also differences in the serum titers for measles IgG antibody, which were higher in the group of all healthy sibs than in healthy volunteers, and (as with CSF titers) higher in the subgroup of healthy sibs with two or more 2 CSF-enriched OCBs than the other sibs. Thus a significant proportion of healthy siblings to MS patients have a partially hyperimmune condition similar to that occurring in MS, which in 19% manifested itself as an OCB reaction, in 9% as increased CSF measles IgG antibody titers, and in 21% as increased serum measles IgG antibody titers, these phenomena tending to occur in the same individuals. This condition is characterized by CSF-enriched OCBs with undefined specificity, although some increased antiviral reactivity is found both in the serum and CSF. While it needs further characterization, a genetic trait interacting with common infections is suggested. The recurrence risk of this condition is approximately five times higher than the 3-4% recurrence risk for manifest MS reported for sibs.
39.	Haghighi, Sara, et al. (författare) Increased CSF sulfatide levels and serum glycosphingolipid antibody levels in healthy siblings of multiple sclerosis patients 2013 Ingår i: Journal of the Neurological Sciences. - : Elsevier BV. - 0022-510X .- 1878-5883. ; 326:1-2, s. 35-39 Tidskriftsartikel (refereegranskat)abstract A proportion of healthy siblings of multiple sclerosis (MS) patients have an oligodonal immunological reaction in their cerebrospinal fluid (CSF) termed the "MS oligoclonal trait". The CSF levels of the major myelin glycosphingolipid sulfatide and serum antibodies against the glycosphingolipids sulfatide and galactosylceramide were recently reported to be increased in MS patients. We studied the levels of these substances in pairs of 46 patients and their 46 healthy siblings and 50 unrelated healthy blood donors (HBD). The sulfatide concentration in CSF was assayed by thin layer chromatography and immunostaining, and the concentration of galactosylceramide by densitometry after thin layer chromatography. Anti-glycosphingolipid antibody levels were assayed by ELISA. In the healthy siblings, the CSF sulfatide concentrations were markedly increased (p<0.001, age adjusted p = 0.025), and the serum IgM anti-GalCer antibodies were increased in healthy siblings compared with HBD (p = 0.02). The increased sulfatide or antibody levels did not co-segregate with the "MS oligoclonal trait" or the HLA-DR15 phenotype. In conclusion, a proportion of healthy siblings of MS patients have increased CSF sulfatide and anti-glycosphingolipid antibody levels, which may, analogous to the "MS oligoclonal trait", constitute an "MS glycosphingolipid endophenotype". Endophenotypes could potentially simplify the genetics of complex disorders
40.	Haghighi, Sara, et al. (författare) Myelin glycosphingolipid immunoreactivity and CSF levels in multiple sclerosis. 2012 Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 125:1, s. 64-70 Tidskriftsartikel (refereegranskat)abstract Objectives- Patients with multiple sclerosis were reported to harbour antibodies not only against proteins and glycoproteins but also against glycolipids, including sulfatide and galactosylceramide (GalCer), the two major glycosphingolipids of myelin. However, previous results were inconsistent concerning glycosphingolipid levels, antibody type, dominance of serum or Cerebrospinal fluid compartments and relationship to the multiple sclerosis (MS) course. Results- We hereby report that the cerebrospinal fluid levels of sulfatide were increased in patients with MS (n=46) compared with controls (n=50, P<0.001). In addition, patients had higher serum IgM anti-glycosphingolipid titres than controls (P=0.03 for sulfatide, <0.001 for GalCer), while the anti-glycosphingolipid IgM antibodies in the cerebrospinal fluid were essentially normal. However, in seven of 46 patients cerebrospinal fluid IgG antibodies against GalCer (P=0.004) could be detected, which was not found in any of the control individuals, and this finding might mirror the occurrence of more specific B-cell clones behind the blood-brain barrier. Conclusions- The IgM immunoreactivity in serum did not show any relationship to the type of course or severity of MS, arguing against a phenomenon secondary to myelin damage. Thus, the IgM antibody findings are compatible with an early antigen challenge or autoimmunity associated with natural antibodies.
41.	Hansson, Sarah, 1976, et al. (författare) Cystatin C in cerebrospinal fluid and multiple sclerosis. 2007 Ingår i: Annals of neurology. - : Wiley. - 0364-5134. ; 62:2, s. 193-196 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: A recent study using surface-enhanced laser desorption/ionization time-of-flight analysis of cerebrospinal fluid identified a 12.5 kDa truncated isoform of cystatin C (CysC) as a specific biomarker for multiple sclerosis (MS). METHODS: Surface-enhanced laser desorption/ionization time-of-flight analysis of cerebrospinal fluid samples from 43 MS patients and 46 healthy control subjects. RESULTS: Full-length CysC (13.4 kDa) concentration was similar in MS and control samples. The 12.5 kDa CysC protein was produced from full-length CysC by N-terminal cleavage during storage at -20 degrees C. INTERPRETATION: The 12.5 kDa CysC isoform is a storage-related artifact and is not useful as a diagnostic marker for MS.
42.	Hartelius, Lena, 1957, et al. (författare) How does fatigue affect communication? The influence of fatigue on cognitive, physical, psychosocial and communicative ability in individuals with multiple sclerosis 2004 Ingår i: International Journal of MS Care. ; 6, s. 39-51 Tidskriftsartikel (refereegranskat)
43.	Hensiek, A E, et al. (författare) Familial effects on the clinical course of multiple sclerosis. 2007 Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 1526-632X .- 0028-3878. ; 68:5, s. 376-83 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Familial factors influence susceptibility to multiple sclerosis (MS) but it is unknown whether there are additional effects on the natural history of the disease. METHOD: We evaluated 1,083 families with > or =2 first-degree relatives with MS for concordance of age at onset, clinical course, and disease severity and investigated transmission patterns of these clinical features in affected parent-child pairs. RESULTS: There is concordance for age at onset for all families (correlation coefficient 0.14; p < 0.001), as well as for affected siblings (correlation coefficient 0.15; p < 0.001), and affected parent-child pairs (correlation coefficient 0.12; p = 0.03) when each is evaluated separately. Concordance for year of onset is present among affected siblings (correlation coefficient 0.18; p < 0.001) but not the parent-child group (correlation coefficient 0.08; p = 0.15). The clinical course is similar between siblings (kappa 0.12; p < 0.001) but not affected parents and their children (kappa -0.04; p = 0.09). This influence on the natural history is present in all clinical subgroups of relapsing-remitting, and primary and secondary progressive MS, reflecting a familial effect on episodic and progressive phases of the disease. There is no concordance for disease severity within any of the considered family groups (correlation coefficients: all families analyzed together, 0.02, p = 0.53; affected sibling group, 0.02, p = 0.61; affected parent-child group, 0.02, p = 0.69). Furthermore, there are no apparent transmission patterns of any of the investigated clinical features in affected parent-child pairs and no evidence for anticipation or effects of genetic loading. CONCLUSION: Familial factors do not significantly affect eventual disease severity. However, they increase the probability of a progressive clinical course, either from onset or after a phase of relapsing remitting disease. The familial effect is more likely to reflect genetic than environmental conditions. The results are relevant for counseling patients and have implications for the design of studies seeking to identify factors that influence the natural history of the disease.
44.	Jons, Daniel, 1974, et al. (författare) Axonal injury in asymptomatic individuals preceding onset of multiple sclerosis 2022 Ingår i: Annals of Clinical and Translational Neurology. - : Wiley. - 2328-9503. ; 9:6, s. 882-887 Tidskriftsartikel (refereegranskat)abstract Axonal loss is the main cause of irreversible disability in multiple sclerosis (MS). Serum neurofilament light (sNfL) is a biomarker of axonal disintegration. In this nested case-control study, blood samples from 519 presymptomatic persons (age range 4-39 years) who later received an MS diagnosis showed higher sNfL concentrations than 519 matched controls (p < 0.0001), noticeable at least 10 years before clinical MS onset. Mean values for pre-MS and control groups were 9.6 pg/mL versus 7.4 pg/mL 0-5 years before onset, and 6.4 pg/mL versus 5.8 pg/mL 5-10 years before onset. These results support that axonal injury occurs early in MS pathogenesis.
45.	Jons, Daniel, 1974, et al. (författare) Early hematopoiesis in multiple sclerosis patients 2016 Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728. ; 299, s. 158-163 Tidskriftsartikel (refereegranskat)abstract Contemporary evidence supports that MS immunopathology starts in the peripheral lymphatic system. However, the site and character of crucial initiating events are unknown. We examined subsets of the first stages of blood cells in the bone marrow of 9 MS patients and 11 neurologically healthy controls using FACS analysis. The proportion of natural killer T cells was lower (P = 0.045) in the bone marrow of MS patients, but proportions of hematogenous stem cells, myeloblasts, and B cell precursor subsets in the bone marrow did not differ between MS patients and controls. In this pilot study with a limited number of samples we found no deviation of the early B cell lineage in bone marrow from MS patients. (C) 2016 Elsevier B.V. All rights reserved.
46.	Jons, Daniel, 1974, et al. (författare) Follow-up after infectious mononucleosis in search of serological similarities with presymptomatic multiple sclerosis 2021 Ingår i: Multiple Sclerosis and Related Disorders. - : Elsevier BV. - 2211-0348 .- 2211-0356. ; 56 Tidskriftsartikel (refereegranskat)abstract Background: : A two- to three-fold increase in the risk of multiple sclerosis (MS) after infectious mononucleosis (IM) has been observed in cohort and case control studies. However, this association has not been investigated prospectively from IM. It remains to be determined whether long-term immunospecific sequelae with features consistent with presymptomatic MS occur after IM. Methods: : Sera were obtained from individuals with acute IM from 2003-2007 (n = 42) and from the same individuals at a follow-up (FU) study approximately 10 years after IM. These were assayed for antibodies against a variety of Epstein-Barr virus (EBV) antigens, including gp350, a novel recombinant glycoprotein from the EBV envelope. Similarly, single-protein antigens were used to assess measles and varicella-zoster reactivity (Ncore and varicella-zoster glycoprotein E [VZVgE]). The FU study also included cerebrospinal fluid (CSF) samples from 21 of these individuals to test for IgG antibodies against the same viral antigens. As controls, CSF and serum samples were obtained from 15 EBV-seropositive volunteers who denied a history of IM, and serum samples were obtained from 24 EBV-seropositive blood donors. Anti-gp350, anti-Ncore and anti-VZVgE IgG levels were also analysed in sera and CSF samples from 22 persons with MS. Results: : The FU assays showed higher anti-gp350 IgG (p = 0.007, univariate) than among healthy controls, with no difference in serum anti-VCA or anti-EBNA1 IgG levels and no difference in anti-gp350 in the CSF samples. Anti-Ncore IgG and anti-VZVgE were higher in acute IM samples (p < 0.001 and p < 0.0001, respectively) than at FU, although anti-Ncore remained heightened in an age-adjusted analysis at FU (p = 0.014) compared to the control group. In the MS group, the serum anti-gp350 and anti-Ncore IgG levels were significantly higher than among the control group, but the anti-VZVgE levels were not. The CSF anti-gp350 and VZVgE levels were slightly higher among persons with MS than among the control group, whereas anti-Ncore IgG was markedly higher in persons with MS than in the control group. Conclusion: : In the present study IM showed certain similarities with MS. Increased anti-gp350 reactivity persisted more than a decade after IM, reminiscent of the established increased anti-EBV reactivity in presymptomatic MS. Acute IM was associated with increased anti-measles and anti-VZV immunoreactivity, similar to the MRZ reaction in MS, with some evidence suggesting that this measles reactivity persisted after a decade.
47.	Jons, Daniel, 1974, et al. (författare) Intrathecal immunoreactivity in people with or without previous infectious mononucleosis 2020 Ingår i: Acta Neurologica Scandinavica. - : John Wiley & Sons. - 0001-6314 .- 1600-0404. ; 142:2, s. 161-168 Tidskriftsartikel (refereegranskat)abstract Objectives: The risk of developing multiple sclerosis (MS) increases (OR: 3.1) after infectious mononucleosis (IM). However, the nature of this link is obscure. We tested the hypothesis that IM might incur long-term sequelae, including low-key inflammatory activity, with characteristics of an MS endophenotype (or presymptomatic trait) and that assays of MS-relevant cyto-/chemokines in the cerebrospinal fluid (CSF) post-IM may show a trend in this direction.Materials and methods: We selected seven CSF cytokines (IL-1b, IL-6, YKL-40, TNF-alpha) or chemokines (IL-8, CCL2, IP-10), representing pro-inflammatory factors previously associated with MS. We assayed the CSF levels of these seven cyto-/chemokines in healthy individuals with a median follow-up time of 10 years after serologically confirmed IM (post-IM group, n = 22), and in healthy controls without a history of IM (n = 19). A group of MS patients (n = 23) were included as reference.Results: The CSF levels of IP-10, YKL-40, and CCL-2 were higher in the post-IM group than in our IM unexposed controls (P = .021, .049, .028). Seven of seven cyto-/chemokine assays showed a trend in the predicted direction (Pof binomial ratio = .008). However, this trend was non-significant in a multivariate test (P = .22). A power analysis indicated that similar studies including a larger cohort would be numerically realistic.Conclusions: These results do not reject the hypothesis that the established epidemiological association between IM and MS results from a stepwise inflammatory propagation from IM sequelae to an MS endophenotype (or presymptomatic trait) in a proportion of IM patients, pending confirmation with adequate power.
48.	Jons, Daniel, 1974, et al. (författare) Seroreactivity against lytic, latent and possible cross-reactive EBV antigens appears on average 10 years before MS induced preclinical neuroaxonal damage 2023 Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ Publishing Group Ltd. - 1468-330X .- 0022-3050. ; 95 Tidskriftsartikel (refereegranskat)abstract Background: Multiple sclerosis (MS) and presymptomatic axonal injury appear to develop only after an Epstein-Barr virus (EBV) infection. This association remains to be confirmed across a broad preclinical time range, for lytic and latent EBV seroreactivity, and for potential cross-reacting antigens. Methods: We performed a case-control study with 669 individual serum samples obtained before clinical MS onset, identified through cross-linkage with the Swedish MS register. We assayed antibodies against EBV nuclear antigen 1 (EBNA1), viral capsid antigen p18, glycoprotein 350 (gp350), the potential cross-reacting protein anoctamin 2 (ANO2) and the level of sNfL, a marker of axonal injury. Results: EBNA1 (latency) seroreactivity increased in the pre-MS group, at 15-20 years before clinical MS onset, followed by gp350 (lytic) seroreactivity (p=0.001-0.009), ANO2 seropositivity appeared shortly after EBNA1-seropositivity in 16.7% of pre-MS cases and 10.0% of controls (p=0.001).With an average lag of almost a decade after EBV, sNfL gradually increased, mainly in the increasing subgroup of seropositive pre-MS cases (p=8.10-5 compared with non-MS controls). Seropositive pre-MS cases reached higher sNfL levels than seronegative pre-MS (p=0.038). In the EBNA1-seropositive pre-MS group, ANO2 seropositive cases had 26% higher sNfL level (p=0.0026). Conclusions: Seroreactivity against latent and lytic EBV antigens, and in a subset ANO2, was detectable on average a decade before the appearance of a gradually increasing axonal injury occurring in the last decade before the onset of clinical MS. These findings strengthen the hypothesis of latent EBV involvement in the pathogenesis of MS.
49.	Jons, Daniel, 1974, et al. (författare) Targeting Epstein-Barr virus infection as an intervention against multiple sclerosis 2015 Ingår i: Acta Neurologica Scandinavica. - : Wiley-Blackwell. - 0001-6314 .- 1600-0404. ; 131:2, s. 69-79 Forskningsöversikt (refereegranskat)abstract We here review contemporary data on genetic and environmental risk factors, particularly Epstein-Barr virus infection, for multiple sclerosis. There is an important immunogenetic etiological factor for multiple sclerosis. However, a general assumption is that immune defense genes are activated by the environment, basically by infections. We contend that the relationship between infectious mononucleosis and multiple sclerosis cannot be completely explained by genetics and inverse causality. Epstein-Barr infection as indicated by positive serology is an obligatory precondition for multiple sclerosis, which is a stronger attribute than a risk factor only. Data on events in the early pathogenesis of multiple sclerosis are cumulating from bio-banks with presymptomatic specimens, but there is only little information from the critical age when Epstein-Barr infection including infectious mononucleosis is acquired, nor on the detailed immunological consequences of this infection in individuals with and without multiple sclerosis. We discuss how focused bio-banking may elaborate a rationale for the development of treatment or vaccination against Epstein-Barr virus infection. A cohort in which intervention against Epstein-Barr infections was performed should be the object of neurological follow-up.
50.	Kneider, Maria, et al. (författare) Sequence analysis of human rhinovirus aspirated from the nasopharynx of patients with relapsing-remitting MS. 2009 Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 15:4, s. 437-42 Tidskriftsartikel (refereegranskat)abstract BackgroundUpper respiratory infections were reported to trigger multiple sclerosis relapses. A relationship between picornavirus infections and MS relapses was recently reported.ObjectiveTo evaluate whether human rhinovirus is associated with multiple sclerosis relapses and whether any particular strain is predominant.MethodNasopharyngeal 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.ResultsWe 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.ConclusionWe 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.

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