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| 7. |
- Burman, Joachim, 1974-
(författare)
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Delaying the inevitable : Are disease modifying drugs for progressive MS worthwhile?
- 2021
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Ingår i: Multiple Sclerosis and Related Disorders. - : Elsevier. - 2211-0348 .- 2211-0356. ; 54
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Ocrelizumab and siponimod have a scientifically proven effect in progressive MS and decrease the risk of disability in the short-term. The primary endpoints in the pivotal trials of ocrelizumab and siponimod were reported as a hazard ratio of 3-month confirmed disability progression, which was reported to be 0.76-0.79. Based on this, both drugs were subsequently licensed for use in patients with progressive multiple sclerosis. Hazard ratios are not easily communicated to patients and therefore the alternative endpoint average postponement of disability was calculated with data from the pivotal trials. After two years of treatment, the average postponement of disability was 16 days per year with ocrelizumab and 19 days with siponimod. Over time, the average postponement of disability reached a plateau, when further treatment added little value. Taken together, these data suggest that these interventions have a short-lived and limited clinical effect in patients with progressive MS.
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| 8. |
- Castelo-Branco, Anna, et al.
(författare)
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Infections in patients with multiple sclerosis : A national cohort study in Sweden
- 2020
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Ingår i: Multiple Sclerosis and Related Disorders. - : Elsevier. - 2211-0348 .- 2211-0356. ; 45
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Multiple sclerosis (MS) patients have an increased risk of infections, but few population-based studies have reported infections occurring in MS in the years immediately after diagnosis.OBJECTIVE: To explore incident infections in MS, stratified by age and sex.METHODS: In a Swedish population-based cohort study 6602 incident MS patients (aged ≥18 years), matched at diagnosis with 61,828 matched MS-free individuals were identified between 1st January 2008 and 31st December 2016, using national registers. Incidence rates (IR) and incidence rate ratios (IRR) with 95% CI were calculated for each outcome.RESULTS: The IRRs were 2.54 (95% CI 2.28-2.83) for first serious infection and 1.61 (1.52-1.71) for first non-serious infection. Compared with MS-free individuals, MS patients had higher IRs for skin, respiratory/throat infections, pneumonia/influenza, bacterial, viral, and fungal infections, with the highest IRR observed for urinary tract/kidney infections (2.44; 2.24-2.66). The cumulative incidence for most of these infections was higher among MS patients than MS-free individuals, both 0 to <5 and 5 to <9 years after index date.CONCLUSION: The burden of infections around the time of MS diagnosis and subsequent infection risk, underscore the need for careful considerations regarding the risk-benefit across different disease-modifying therapies.
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- Conradsson, David Moulaee, et al.
(författare)
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Employment status of people with multiple sclerosis in relation to 10-year changes in functioning and perceived impact of the disease
- 2020
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Ingår i: Multiple Sclerosis and Related Disorders. - : ELSEVIER SCI LTD. - 2211-0348 .- 2211-0356. ; 46
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although it is well known that people with multiple sclerosis (PwMS) retire from work early, little is known about how long-term changes in functioning and perceived impact of multiple sclerosis (MS) interact with sustainability of employment.Objective: To explore changes in functioning and in perceived impact of MS over 10 years, in relation to employment status of PwMS.Methods: In order to measure functioning, data on activities (walking ability, fine hand use, personal activities in daily living); participation in activities of everyday life (domestic, outdoor and leisure activities); body functions (cognitive function, fatigue, depressive symptoms); and perceived impact of MS were collected in 116 PwMS at baseline and at a 10-year follow-up. Ten-year changes were explored with the participants divided into four subgroups based on employment status at the follow-up: 1) full-time work at the 10-year follow-up; 2) part-time work at the 10-year follow-up; 3) declined from working at baseline to not working at the 10-year follow-up; and 4) not working at baseline nor at the 10-year follow-up.Results: Patterns of change in functioning for PwMS who worked showed a more apparent deterioration over 10 years among those working part-time with regard to walking ability, fatigue and depressive symptoms. Members of the subgroups who declined from working at baseline to not working at the 10-year follow-up or who were working neither at baseline nor at the follow-up deteriorated the most in functioning. The subgroup whose employment status declined from baseline to follow-up showed a significant decrease in cognitive function and an increase in perceived physical impact of the disease. All subgroups experienced a deterioration in walking ability over the 10-year span, and in all subgroups a majority had limited fine hand use over the span of the study period.Conclusion: The deterioration in functioning was most apparent in those PwMS whose employment status declined from working at baseline to not working at the 10-year follow-up. Close monitoring of work situation and frequency of activities and participation in everyday activities, as well as recurrent training of functioning, are suggested for maintaining a high level of functioning and work status, or for supporting transition to an appropriate number of working hours.
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| 12. |
- Eklund, Anna, et al.
(författare)
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Original OCT and VEP correlate to disability in secondary progressive multiple sclerosis
- 2022
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Ingår i: Multiple Sclerosis and Related Disorders. - : ELSEVIER SCI LTD. - 2211-0348 .- 2211-0356. ; 68
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Tidskriftsartikel (refereegranskat)abstract
- Background: The afferent visual pathway provides a unique opportunity to monitor clinical and subclinical optic neuritis and features of neuroaxonal degeneration in secondary progressive MS.Objective: To investigate the usefulness of visual evoked potentials (VEP) and optical coherence tomography (OCT) in evaluating SPMS, and the association between these modalities and clinical course and lesion load on the magnetic resonance imaging (MRI) in patients with SPMS with or without a history of optic neuritis (ON). Methods: SPMS patients (n = 27) underwent clinical assessment with Expanded Disability Status Scale (EDSS) grading, visual acuity, OCT, and VEP examination. MRI of the brain and spinal cord were evaluated. Ordinal scores of VEP and MRI findings were used in the statistical analyses.Results: The ganglion cell and inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL) thickness correlated with VEP latency. VEP P100 score correlated with EDSS. Linear regression showed an association between GCIPL thickness and EDSS as well as VEP P100 latency and EDSS. The MRI analyses were negative.Conclusion: VEP latency and GCIPL thickness correlated with disability measured as EDSS in patients with SPMS and are useful in monitoring SPMS patients.
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- Englund, Simon, et al.
(författare)
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Predictors of patient-reported fatigue symptom severity in a nationwide multiple sclerosis cohort
- 2023
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Ingår i: Multiple Sclerosis and Related Disorders. - : Elsevier. - 2211-0348 .- 2211-0356. ; 70
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Fatigue is a debilitating symptom of multiple sclerosis (MS), but its relation to sociodemographic and disease-related characteristics has not been investigated in larger studies. The objectives of this study were to evaluate predictors of self-reported fatigue in a Swedish nationwide register-based MS cohort.METHODS: Using a repeated cross-sectional design, we included 2,165 persons with relapsing- remitting and secondary progressive MS with one or multiple Fatigue Scale for Motor and Cognitive Functions (FSMC) scores, which was modelled using multivariable linear regressions for multiple predictors.RESULTS: Only associations to expanded disability status scale (EDSS) and Symbol Digit Modalities Test (SDMT) were considered clinically meaningful among MS-associated characteristics in our main model; compared to mild disability (EDSS 0-2.5), those with severe disability (EDSS ≥6) scored 17.6 (95% CI 13.1-22.2) FSMC points higher, while the difference was 10.7 (95% CI 8.0-13.4) points for the highest and lowest quartiles of SDMT. Differences between highest and lowest quartiles of health-related quality of life (HRQoL) instruments were even greater and considered clinically meaningful; EuroQoL Visual Analogue Scale (EQ-VAS) 31.9 (95% CI 29.9-33.8), Multiple Sclerosis Impact Scale (MSIS-29) psychological component 35.6 (95% CI 33.8-37.4) and MSIS-29 physical component 45.5 (95% CI 43.7-47.4).CONCLUSION: Higher self-reported fatigue is associated with higher disability level and worse cognitive processing speed, while associations to other MS-associated characteristics including MS type, line of disease modifying therapy (DMT), MS duration, relapse and new cerebral lesions are weak. Furthermore, we found a strong correlation between high fatigue rating and lower ratings on health-related quality of life instruments.
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| 15. |
- Fagius, Jan, et al.
(författare)
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Discontinuation of disease modifying treatments in middle aged multiple sclerosis patients : First line drugs vs natalizumab
- 2017
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Ingår i: Multiple Sclerosis and Related Disorders. - : Elsevier BV. - 2211-0348 .- 2211-0356. ; 12, s. 82-87
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Several disease-modifying drugs (DMD) are available for the treatment of MS, and most patients with relapsing-remitting disease are currently treated. Data on when and how DMD treatment can be safely discontinued are scarce.METHODS: Fifteen MS patients, treated with natalizumab for >5 years without clinical and radiological signs of inflammatory disease activity, suspended treatment and were monitored with MRI examinations and clinical follow-up to determine recurrence of disease activity. This group was compared with a retrospectively analysed cohort comprising 55 MS patients treated with first-line DMDs discontinuing therapy in the time period of 1998-2015 after an analogous stable course.RESULTS: Natalizumab discontinuers were followed for on average 19 months, and follow-up data for 56 months were available for first-line DMD quitters. Two-thirds of natalizumab treated patients experienced recurrent inflammatory disease activity, and one third had recurrence of rebound character. In contrast, 35% of first-line DMD quitters had mild recurrent disease activity, and no one exhibited rebound.CONCLUSIONS: Withdrawal of a first-line DMD after prolonged treatment in middle-aged MS patients with stable disease appears to be relatively safe, while natalizumab withdrawal in a similar group of patients cannot be safely done without starting alternative therapy.
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| 16. |
- Gaetani, Lorenzo, et al.
(författare)
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Cerebrospinal fluid neurofilament light chain predicts disease activity after the first demyelinating event suggestive of multiple sclerosis
- 2019
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Ingår i: Multiple Sclerosis and Related Disorders. - : Elsevier BV. - 2211-0348 .- 2211-0356. ; 35, s. 228-232
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prediction of disease activity in patients with a first demyelinating event suggestive of multiple sclerosis (MS) is of high clinical relevance. Cerebrospinal fluid (CSF) neurofilament light chain (NfL) has shown to have prognostic value in MS patients. In this work, we measured CSF NfL in patients at the first demyelinating event in order to find a cut-off value able to discriminate patients who will have disease activity from those who will remain stable during the follow-up. Methods: We included CSF samples collected within 30 days after the onset of the first demyelinating event from 32 patients followed-up for 3.8 ± 2.5 years. CSF NfL was measured with a newly developed in-house enzyme linked immunosorbent assay (ELISA). Results: At the first demyelinating event, patients with subsequent disease activity had significantly higher baseline CSF NfL values compared to clinically and radiologically stable patients (median 812.5 pg/mL, range 205–2359 pg/mL vs 329.5 pg/mL, range 156–3492 pg/mL, p = 0.002). A CSF NfL cut-off value of 500 pg/mL significantly discriminated these two groups of patients with a 90% sensitivity and an 83.3% specificity. Conclusion: Our results confirm that CSF NfL is a prognostic marker in the very early phases of MS. The validation of a cut-off value of 500 pg/mL could provide clinicians with a dichotomous variable that can simplify the prognostic assessment of patients at the first demyelinating event.
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| 18. |
- Hestvik, Anne Lise K., et al.
(författare)
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Real-world study of relapsing-remitting multiple sclerosis patients treated with Teriflunomide in Nordic countries: Quality-Of-Life, efficacy, safety and adherence outcomes
- 2022
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Ingår i: Multiple Sclerosis and Related Disorders. - : ELSEVIER SCI LTD. - 2211-0348 .- 2211-0356. ; 63
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Tidskriftsartikel (refereegranskat)abstract
- Background: Teriflunomide 14 mg (Aubagio (R)) is a once-daily, oral drug approved for the treatment of relapsing forms of multiple sclerosis (MS). While the efficacy and safety of teriflunomide have been thoroughly characterised across an extensive clinical program, we were interested in studying performance of the drug with respect to quality-of-life (QoL) outcomes in persons with MS in a real-world setting. Methods: Teri-LIFE was a prospective, open label, non-interventional, observational, multi-centre study that enrolled 200 teriflunomide-treated patients from three Nordic countries. The primary outcome measure changes in patient-reported QoL over 24 months as measured by the Short Form-36 (SF-36) questionnaire. Secondary endpoints included clinical efficacy, fatigue, safety, treatment satisfaction (Treatment Satisfaction Questionnaire for Medication version 1.4 (TSQM-1.4)), treatment adherence, and health economic outcomes. Most assessments were made at baseline and then at 6-monthly intervals. Results: Overall, changes in SF-36 scores from baseline to last visit indicated a stable QoL during treatment with teriflunomide for up to 24 months. Relapse activity decreased during the study compared to the pre-baseline period (p<0.001), patient-reported disability increased marginally, and no substantial change was seen in fatigue scores. The mean scores for TSQM domains increased nominally though not significantly from Month 6 to Month 24. The convenience and side effects TSQM domains recorded the highest median scores, indicating the acceptability of oral teriflunomide in this cohort. This was reflected in a generally high treatment adherence and decreased healthcare utilization during the study period. Some differences were seen between treatment-naive and previously treated patients, likely reflecting different patient demographics and disease status at study entry, along with different treatment expectations. Conclusion: Teri-LIFE offers a reliable snapshot of QoL, efficacy, safety, and health economic outcomes in persons with relapsing MS treated with teriflunomide in routine clinical practice in Nordic countries The results were consistent with previous clinical trials and real-world studies.
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| 19. |
- Hiyoshi, Ayako, 1972-, et al.
(författare)
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Myopia in late adolescence and subsequent multiple sclerosis among men
- 2023
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Ingår i: Multiple Sclerosis and Related Disorders. - : Elsevier. - 2211-0348 .- 2211-0356. ; 71
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Risk factors such as low vitamin D level has been implicated in the etiology of multiple sclerosis (MS) and may be relevant to myopia, such that there may be an association between myopia and MS.METHODS: Using linked Swedish national register data, we conducted a cohort study of men who were born in Sweden between 1950 and 1992, lived in Sweden between 1990 and 2018, and enrolled in military conscription assessment (n = 1,847,754). Myopia was defined based on the spherical equivalent refraction measured at conscription assessment, around age 18 years. Multiple sclerosis was identified using the Patient Register. Cox regression produced hazard ratios (HR) with 95% confidence intervals (95% CI), with adjustment for demographic and childhood socioeconomic characteristics and residential region. Due to changes in the assessment of refractive error, the analysis was stratified into two groups by the year of conscription assessment: 1969-1997 and 1997-2010.RESULTS: Among 1,559,859 individuals during a maximum of 48 years of follow-up from age 20 to 68 years (44,715,603 person-years), there were 3,134 MS events, and the incidence rate 7.0 (95% CI [6.8, 7.3] per 100,000 person-years). Among individuals with conscription assessments during 1997-2010, there were 380 MS events. There was no evidence of an association between myopia and MS, with HR 1.09 (95% CI 0.83, 1.43). Among individuals who underwent conscription assessment in 1969-1997, there were 2754 MS events. After adjusting for all covariates, there was no evidence of an association between myopia and MS (HR 0.99 [95% CI 0.91, 1.09]).CONCLUSION: Myopia in late adolescence is not associated with a subsequent raised risk of MS and thus there does not appear to be important shared risk factors.
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| 20. |
- Hojjati, Sara, et al.
(författare)
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Dimethyl fumarate treatment in relapsing remitting MS changes the inflammatory CSF protein profile by a prominent decrease in T-helper 1 immunity
- 2023
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Ingår i: Multiple Sclerosis and Related Disorders. - : ELSEVIER SCI LTD. - 2211-0348 .- 2211-0356. ; 80
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dimethyl fumarate (DMF) is a common treatment for multiple sclerosis (MS), but its mechanisms of action are not fully understood. Targeted proteomics offers insights into effects of DMF and biomarkers for treatment responses.Objectives: To assess influence of DMF on inflammation-and neuro-associated proteins in plasma and cerebro-spinal fluid (CSF) in MS and to reveal biomarkers for predicting treatment responses.Methods: Using the high-sensitivity and high-specificity method of proximity extension assay (PEA), we measured 182 inflammation-and neuro-associated proteins in paired plasma (n = 28) and CSF (n = 12) samples before and after one year of DMF treatment. Disease activity was evaluated through clinical examination and MRI. Statistical tests, network analysis, and regression models were used.Results: Several proteins including T-helper 1 (Th1)-associated proteins (CXCL10, CXCL11, granzyme A, IL-12p70, lymphotoxin-alpha) were consistently decreased in CSF, while IL-7 was increased after one year of treatment. The changes in plasma protein levels did not follow the same pattern as in CSF. Logistic regression models identified potential biomarker candidates (including plexins and neurotrophins) for prediction of treatment response.Conclusions: DMF treatment induced prominent changes in CSF proteins, consistently reducing Th1-associated pro-inflammatory proteins. Neurodegeneration-related CSF proteins were able to predict treatment response. Protein biomarkers hold promise for personalized medicine.
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| 21. |
- Hrnciarova, T., et al.
(författare)
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Does initial high efficacy therapy in multiple sclerosis surpass escalation treatment strategy? A comparison of patients with relapsing-remitting multiple sclerosis in the Czech and Swedish national multiple sclerosis registries
- 2023
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Ingår i: Multiple Sclerosis and Related Disorders. - 2211-0348 .- 2211-0356. ; 76
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Tidskriftsartikel (refereegranskat)abstract
- Background: In relapsing-remitting multiple sclerosis (RRMS) the most common treatment strategy has been to start with low-moderate efficacy disease modifying therapy (LE-DMT) and to escalate to more efficacious treatments in cases of breakthrough disease activity. However, recent evidence suggests a better outcome in patients commencing with moderate-high efficacy DMT (HE-DMT) immediately after clinical onset.Objective: The aim of this study is to compare disease activity and disability outcomes in patients treated with the two alternative strategies using the Swedish and Czech national multiple sclerosis registries, taking advantage of the fact that the relative frequency of each strategy differs markedly between these two countries. Methods: Adult RRMS patients who initiated their first-ever DMT between 2013 and 2016 and were included in the Swedish MS register were compared with a similar cohort from the MS register of the Czech Republic using propensity score overlap weighting as a balancing method. The main outcomes of interest were time to confirmed disability worsening (CDW), time to achieve an expanded disability status scale (EDSS) value of 4, time to relapse, and time to confirmed disability improvement (CDI). To support the results, a sensitivity analysis focusing solely on patients from Sweden starting with HE-DMT and patients from the Czech Republic starting with LE-DMT was performed.Results: In the Swedish cohort, 42% of patients received HE-DMT as initial therapy compared to 3.8% of patients in the Czech cohort. The time to CDW was not significantly different between the Swedish and Czech cohorts (p-value 0.2764), with hazard ratio (HR) of 0.89 and a 95% confidence interval (CI) of 0.77-1.03. Patients from the Swedish cohort exhibited better outcomes for all remaining variables. The risk of reaching EDSS 4 was reduced by 26% (HR 0.74, 95%CI 0.6-0.91, p-value 0.0327), the risk of relapse was reduced by 66% (HR 0.34, 95%CI 0.3-0.39, p-value <0.001), and the probability of CDI was three times higher (HR 3.04, 95%CI 2.37-3.9, p-value <0.001).Conclusion: The analysis of the Czech and the Swedish RRMS cohorts confirmed a better prognosis for patients in Sweden, where a significant proportion of patients received HE-DMT as initial treatment.
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| 23. |
- Håkansson, Irene, et al.
(författare)
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Fatigue scores correlate with other self-assessment data, but not with clinical and biomarker parameters, in CIS and RRMS
- 2019
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Ingår i: Multiple Sclerosis and Related Disorders. - : ELSEVIER SCI LTD. - 2211-0348 .- 2211-0356. ; 36
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fatigue is common in multiple sclerosis and is associated with reduced quality of life. This study aimed to assess the correlation between fatigue scores and data from other self-assessment questionnaires, neuropsychological tests and neuroimaging, as well as data on neuroimmunological markers in cerebrospinal fluid (CSF) and serum/plasma, in clinically isolated syndrome (CIS) and relapsing remitting MS (RRMS). Methods: Modified fatigue impact scale (MFIS) scores were determined in 38 patients with newly diagnosed CIS or RRMS at baseline and after one year in a prospective longitudinal cohort study. Non-parametric correlation analyses were used to assess associations between MFIS scores and other self-assessment questionnaire data (Hospital Anxiety and Depression scale (HAD), Multiple Sclerosis Impact Scale 29 (MSIS-29) and Short Form 36 (SF-36)), as well as with neuropsychological test performances (e.g. Auditory Consonant Trigram Test (ACTT)), clinical parameters (e.g. disease duration and expanded disability status scale (EDSS)), magnetic resonance imaging (MRI) data (number of T2 lesions in brain MRI and total brain volume) and several neurodegenerative/neuroinflammatory markers in CSF and serum/plasma (IL-1 beta, IL-6, CXCL1, CXCL10, CXCL13, CCL-22 in plasma; neurofilament light chain (NFL) in serum; IL-6, CXCL1, CXCL10, CXCL13, CCL22, NFL and chitinase-3-like-1 (CHI3L1) in CSF. CSF and serum/plasma from 21 age- and sex-matched healthy controls were available for comparison. Results: At both baseline and one-year follow-up, fatigue scores correlated significantly with HAD, MSIS-29 and SF-36 scores and ACTT performance (Spearmans rho 0.45-0.78, all p amp;lt;= 0.01) but not with the other neuropsychological test results, disease duration, EDSS ratings, number of T2 lesions, total brain volume or neurodegenerative/neuroinflammatory markers, including neurofilament light chain levels in CSF and serum. In group comparisons, MFIS scores were similar in patients fulfilling no evidence of disease activity-3 (NEDA-3) (n = 18) and patients not fulfilling NEDA-3 (n = 20) during one year of follow-up (p amp;gt; 0.01). Conclusions: In this cohort of patients with newly diagnosed CIS and RRMS, fatigue scores were associated with mood, disease impact on daily life and quality of life as well as with alterations of attentive functions. Study results indicate that subjective fatigue scores are not well reflected by some commonly used and objectively measurable disease parameters like EDSS, T2 lesions and NFL levels.
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| 25. |
- Jons, Daniel, 1974, et al.
(författare)
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Follow-up after infectious mononucleosis in search of serological similarities with presymptomatic multiple sclerosis
- 2021
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Ingår i: Multiple Sclerosis and Related Disorders. - : Elsevier BV. - 2211-0348 .- 2211-0356. ; 56
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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.
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| 26. |
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| 27. |
- Katsarogiannis, Evangelos, et al.
(författare)
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Evoked potentials after autologous hematopoietic stem cell transplantation for multiple sclerosis
- 2024
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Ingår i: Multiple Sclerosis and Related Disorders. - : Elsevier. - 2211-0348 .- 2211-0356. ; 83
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the effect of autologous hematopoietic stem cell transplantation (AHSCT) on functional aspects of the nervous system assessed by visual (VEP), somatosensory (SEP), and motor (MEP) evoked potentials in patients with relapsing -remitting multiple sclerosis. Background: Several studies have demonstrated the efficacy of AHSCT on inflammatory activity and disability progression in patients with multiple sclerosis. However, the impact of AHSCT on evoked potentials has not been evaluated before. Methods: Twelve AHSCT-treated patients from Uppsala University Hospital were consecutively recruited. Evoked potentials (EP) were collected at baseline and two follow-up visits, 3 and 12 months post-AHSCT. We calculated a composite EP score for each participant and compared it between different time points. Results: The median total EP score decreased from 5 at baseline, to 2.5 at 12 months post-ASHCT (p = 0.008). A significant improvement in tibial SEP (tSEP) latencies was observed (42.7 vs 41.5 ms, p < 0.001), with a similar trend for MEP latencies 12 months post-ASHCT. No significant changes in median SEP or VEP latencies were observed. Conclusions: Treatment with AHSCT was associated with improved transmission in some central nervous system pathways in multiple sclerosis patients.
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| 28. |
- Korjagina, Marta, et al.
(författare)
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Prevalence of adverse pregnancy outcomes after exposure to interferon beta prior to or during pregnancy in women with MS : Stratification by maternal and newborn characteristics in a register-based cohort study in Finland and Sweden
- 2020
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Ingår i: Multiple Sclerosis and Related Disorders. - : Elsevier. - 2211-0348 .- 2211-0356. ; 48
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Previous studies reported no increase in the prevalence of adverse pregnancy outcomes after exposure to interferon-beta (IFN-beta). However, no study has investigated if the prevalence of these outcomes after IFN-beta exposure is modified by maternal and newborn characteristics. Our objective was to describe the stratified prevalence of adverse pregnancy outcomes among women with multiple sclerosis (MS) exposed only to IFN-beta or unexposed to any MS disease modifying drugs (MSDMDs).METHODS: This population-based cohort study using Finnish (1996-2014) and Swedish (2005-2014) register data included pregnancies of women with MS exposed only to IFN-beta 6 months before or during pregnancy (n=718) or unexposed to MSDMDs (n=1397). The outcome prevalences were described stratified by maternal and newborn characteristics, with 95% confidence intervals (CIs). Confounder-adjusted analyses were performed if the prevalence results indicated modified effect of IFN-beta in specific strata.RESULTS: The stratified analysis indicated that the prevalence of serious (anomaly or stillbirth) and other adverse pregnancy outcomes was similar among the exposed and unexposed, with no statistically significant difference. Among women treated for MS >5 years, serious adverse pregnancy outcomes occurred in 4.3% (95%CI: 1.9-8.3%) of pregnancies exposed only to IFN-beta 6 months before or during pregnancy and in 2.7% (95%CI: 1.2-5.0%) of unexposed pregnancies. The confounder adjusted analyses did not support the hypothesis that MS treatment duration before pregnancy would modify the risk of adverse pregnancy outcomes after exposure to IFN-beta 6 months before or during pregnancy.CONCLUSION: The prevalence of adverse pregnancy outcomes was not increased after IFN-beta exposure, when pregnancies of women with MS were stratified by maternal and newborn characteristics. The stratified results were similar to the unstratified results in the same population.
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| 29. |
- Kågström, S., et al.
(författare)
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Reduction of the risk of PML in natalizumab treated MS patients in Sweden: An effect of improved PML risk surveillance
- 2021
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Ingår i: Multiple Sclerosis and Related Disorders. - : Elsevier BV. - 2211-0348 .- 2211-0356. ; 50
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Tidskriftsartikel (refereegranskat)abstract
- Background: Natalizumab (NTZ) treatment of multiple sclerosis (MS) has been associated with increased risk of progressive multifocal leukoencephalopathy (PML). The aim of the present study was to evaluate the impact of PML risk assessment on PML incidence in NTZ treated MS patients. Methods: By using information from the population-based Swedish MS registry a retrospective cohort was established of patients treated with NTZ between 2006-2018. The effect on PML incidence before and after utilizing a risk management plan, including JC virus (JCV) serology, was analyzed. Results: In December 2018, 804 PML cases associated with NTZ therapy of MS had been reported globally, including 9 cases from Sweden. The estimated PML incidence 2018 in Sweden and globally was 0.7 (0.3-1.4) and 4.15 (3.9-4.4) per 1,000 person years, respectively. In Sweden, JCV serology was introduced 2012 for PML risk assessment and the cumulative risk of PML was significantly lower 2012-2018 compared to the period 2006-2011 (p=0.042). The mean NTZ exposure time was 60.1 months (SD 37.2) in the first period (2006-2011) and 32.6 months (SD 22.0) in the second period (2012-2018). The number of patients treated with NTZ decreased, and the number of patients at increased risk of PML was 1.9 % at the end of the study period. Conclusion: Since 2006 the incidence of PML associated with NTZ treatment of MS has decreased in Sweden. Our findings suggest that this reduction is due to an effective adoptation and adherence to the established risk management plan that implies switching patients at increased PML risk from NTZ to other highly efficacious therapies. A less pronounced decline in PML incidence has recently been observed in France, but not globally. © 2021 The Authors
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| 31. |
- Mahamud, Zamzam, et al.
(författare)
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Prognostic impact of epilepsy in multiple sclerosis
- 2020
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Ingår i: Multiple Sclerosis and Related Disorders. - : Elsevier BV. - 2211-0348 .- 2211-0356. ; 38
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Tidskriftsartikel (refereegranskat)abstract
- Background: The incidence of epilepsy, a disease generally associated with increased morbidity and mortality, is increased in multiple sclerosis (MS) but its impact on MS prognosis is largely unknown. Objectives: To investigate the association between acquired epilepsy and mortality in MS and to examine the occurrence of epilepsy as a stated cause of death in MS. To examine the association between acquired epilepsy and subsequent conversion to secondary progressive MS (SPMS). Methods: Using the Swedish MS register, we conducted a nationwide register-based cohort study including 10,383 patients with MS onset between 31/12/1991 and 31/12/2014, and with no history of epilepsy before MS onset. Data on epilepsy diagnosis and cause of death (COD) were extracted from comprehensive national registers. Cox regression was used to estimate hazard ratios (HR) of death stratified by MS course, and SPMS conversion after epilepsy diagnosis. The HRs were adjusted for age at MS onset and sex. Results: The adjusted HR of death after epilepsy diagnosis for unselected MS patients was 3.85 (95% CI: 2.53–5.85). Stratifying by disease course, the adjusted HR of death after epilepsy diagnosis in primary progressive MS was 2.28 (95% CI: 0.99–5.26) and in relapsing-onset MS (ROMS), 5.48 (95% CI: 3.33–9.04). Further subdivision of ROMS revealed the adjusted risk of death after epilepsy diagnosis in relapsing remitting MS to be 3.84 (95% CI: 1.57–9.42) and 6.66 (95% CI: 3.18–13.92) in SPMS. Epilepsy was the underlying COD in 4.55% of MS patients with epilepsy. The majority (50%) of MS patients with epilepsy had MS as their stated underlying COD. Adjusted HR of conversion to SPMS after epilepsy diagnosis was 0.83 (95% CI: 0.45–1.56). Conclusion: Epilepsy in MS is associated with increased mortality although death from epilepsy is rare. Most MS patients with epilepsy died of MS, and epilepsy was most lethal when developed in SPMS. We thus suggest that development of epilepsy is a marker of severe MS. Despite this, we found no association between epilepsy and conversion to SPMS. © 2019 Elsevier B.V.
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| 32. |
- Marisa, Ferreira, 1992-, et al.
(författare)
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Using endogenous saccades to characterize fatigue in multiple sclerosis
- 2017
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Ingår i: Multiple Sclerosis and Related Disorders. - : Elsevier. - 2211-0348 .- 2211-0356. ; 14, s. 16-22
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Tidskriftsartikel (refereegranskat)abstract
- PurposeMultiple Sclerosis (MS) is likely to cause dysfunction of neural circuits between brain regions increasing brain working load or a subjective overestimation of such working load leading to fatigue symptoms. The aim of this study was to investigate if saccades can reveal the effect of fatigue in patients with MS.MethodsPatients diagnosed with MS (EDSS<=3) and age matched controls were recruited. Eye movements were monitored using an infrared eyetracker. Each participant performed 40 trials in an endogenous generated saccade paradigm (valid and invalid trials). The fatigue severity scale (FSS) was used to assess the severity of fatigue. FSS scores were used to define two subgroups, the MS fatigue group (score above normal range) and the MS non-fatigue. Differences between groups were tested using linear mixed models.ResultsThirty-one MS patients and equal number of controls participated in this study. FSS scores were above the normal range in 11 patients. Differences in saccade latency were found according to group (p<0.001) and trial validity (p=0.023). Differences were 16.9 ms, between MS fatigue and MS non-fatigue, 15.5 ms between MS fatigue and control. The mean difference between valid and invalid trials was 7.5 ms. Differences in saccade peak velocity were found according to group (p<0.001), the difference between MS fatigue and control was 22.3°/s and between MS fatigue and non-fatigue was 12.3°/s. Group was a statistically significant predictor for amplitude (p<0.001). FSS scores were correlated with peak velocity (p=0.028) and amplitude (p=0.019).ConclusionConsistent with the initial hypothesis, our study revealed altered saccade latency, peak velocity and amplitude in patients with fatigue symptoms. Eye movement testing can complement the standard inventories when investigating fatigue because they do not share similar limitations. Our findings contribute to the understanding of functional changes induced by MS and might be useful for clinical trials and treatment decisions.
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| 37. |
- Novakova, Lenka, 1984, et al.
(författare)
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NFL and CXCL13 may reveal disease activity in clinically and radiologically stable MS
- 2020
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Ingår i: Multiple Sclerosis and Related Disorders. - : Elsevier BV. - 2211-0348 .- 2211-0356. ; 46
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Tidskriftsartikel (refereegranskat)abstract
- © 2020 Background: Cerebrospinal fluid (CSF) levels of neurofilament light (NFL), a biomarker of axonal damage, and CXCL13, a chemokine involved in B-cell regulation, are both associated with disease activity in multiple sclerosis (MS). Objective: To explore the potential of NFL and CXCL13 to detect residual disease activity in patients with no signs of clinical or ongoing radiological activity and to study the clinical relevance of such activity. Methods: NFL and CXCL13 concentrations were determined with ELISA in CSF obtained from 90 relapsing-remitting (RR) MS and 47 Progressive (Pr) MS (including primary and secondary PrMS) at baseline and after 12 months of follow-up. The patients were assessed at baseline, before initiating or switching disease modifying therapy (DMT) and again after 12 and 27 months of follow-up. Results: All patients with ongoing disease activity (relapse or contrast-enhancing lesions on MRI) had increased NFL or CXCL13. The proportion of RRMS and PrMS patients without ongoing disease activity with elevation of either NFL or CXCL13 (residual disease activity) was 39% and 50%, respectively, and both were increased in 11% and 16%, respectively. The treatment with DMTs decreased the proportion with residual disease activity in both RRMS and PrMS significantly. We could not show any significant association between residual disease activity and clinical or MRI measures at 12 or 27 months of follow-up. Conclusions: Although most of this real-world study population had been treated with second-line DMTs and achieved clinical and radiological stability, a significant proportion of patients still displayed increased CSF levels of both NFL and CXCL13, indicating residual disease activity. Thus, these markers seemed considerably more sensitive to disease activity than clinical and MRI measures. However, the long-term clinical significance of such activity remains to be determined.
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| 40. |
- Pavlovic, Ivan, et al.
(författare)
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Cerebrospinal fluid mtDNA concentrations are increased in multiple sclerosis and were normalized after intervention with autologous hematopoietic stem cell transplantation
- 2024
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Ingår i: Multiple Sclerosis and Related Disorders. - : Elsevier. - 2211-0348 .- 2211-0356. ; 84
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMitochondrial DNA (mtDNA) is a pro-inflammatory damage-associated molecular pattern molecule and could be an early indicator for inflammation and disease activity in MS. Autologous hematopoietic stem cell transplantation (aHSCT) is a potent treatment for MS, but its impact on mtDNA levels in cerebrospinal fluid (CSF) remains unexplored.ObjectivesTo verify elevated CSF mtDNA concentrations in MS patients and assess the impact of aHSCT on mtDNA concentrations.MethodsMultiplex droplet digital PCR (ddPCR) was used to quantify mtDNA and nuclear DNA in 182 CSF samples. These samples were collected from 48 MS patients, both pre- and post-aHSCT, over annual follow-ups, and from 32 healthy controls.ResultsCSF ccf-mtDNA levels were higher in patients with MS, correlated to multiple clinical and analytical factors and were normalized after intervention with aHSCT. Differences before aHSCT were observed with regard to MRI-lesions, prior treatment and number of relapses in the last year prior to aHSCT.ConclusionOur findings demonstrate elevated CSF mtDNA levels in MS patients, which correlate with disease activity and normalize following aHSCT. These results position mtDNA as a potential biomarker for monitoring inflammatory activity and response to treatment in MS.
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| 44. |
- Simon, K. Claire, et al.
(författare)
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Age at Epstein-Barr virus infection and Epstein-Barr virus nuclear antigen-1 antibodies in Swedish children
- 2012
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Ingår i: Multiple Sclerosis and Related Disorders. - : Elsevier BV. - 2211-0348 .- 2211-0356. ; 1:3, s. 136-138
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Tidskriftsartikel (refereegranskat)abstract
- There is strong evidence supporting a role for Epstein-Barr virus (EBV) in the etiopathogenesis of multiple sclerosis (MS). Because of the strong association between antibody (Ab) titer against EBV nuclear antigen 1 (EBNA1) and late age at EBV infection, manifested as infectious mononucleosis (IM), and MS risk, we sought to determine whether age at primary EBV infection was associated with subsequent anti-EBNA1 Ab titer in a longitudinal study of Swedish children with EBV seropositivity and anti-EBNA1 Ab titers measured at ages 2, 5, and 10.
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| 46. |
- Skoog, Bengt, et al.
(författare)
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Continuous prediction of secondary progression in the individual course of multiple sclerosis
- 2014
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Ingår i: Multiple Sclerosis and related Disorders. - : Elsevier BV. - 2211-0348 .- 2211-0356. ; 3:5, s. 584-592
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prediction of the course of multiple sclerosis (MS) was traditionally based on features close to onset. Objective: To evaluate predictors of the individual risk of secondary progression (SP) identified at any time during relapsing-remitting MS. Methods: We analysed a database comprising an untreated MS incidence cohort (n=306) with five decades of follow-up. Data regarding predictors of all attacks (n=749) and demographics from patients (n=157) with at least one distinct second attack were included as covariates in a Poisson regression analysis with SP as outcome. Results: The average hazard function of transition to SPMS was 0.046 events per patient year, showing a maximum at age 33. Three covariates were significant predictors: age, a descriptor of the most recent relapse, and the interaction between the descriptor and time since the relapse. A hazard function termed "prediction score" estimated the risk of SP as number of transition events per patient year (range <0.01 to >0.15). Conclusions: The insights gained from this study are that the risk of transition to SP varies over time in individual patients, that the risk of SP is linked to previous relapses, that predictors in the later stages of the course are more effective than the traditional onset predictors, and that the number of potential predictors can be reduced to a few (three in this study) essential items. This advanced simplification facilitates adaption of the "prediction score" to other (more recent, benign or treated) materials, and allows for compact web-based applications
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| 47. |
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| 48. |
- Sundgren, M., et al.
(författare)
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Cognitive function did not improve after initiation of natalizumab treatment in relapsing-remitting multiple sclerosis. A prospective one-year dual control group study
- 2016
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Ingår i: Multiple Sclerosis and Related Disorders. - : Elsevier BV. - 2211-0348 .- 2211-0356. ; 10, s. 36-43
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cognitive impairment in multiple sclerosis (MS) is common and has severe implications. Natalizumab (NZ) has documented effects on relapse rate and radiological disease activity in relapsing-remitting MS (RRMS) but studies regarding its specific effects on cognitive functioning are few. Previous studies have reported improvement, however, often lacking relevant control groups. The objective of the present study was to evaluate the cognitive effects of NZ treatment, compared to patients on stable first-line treatment and healthy control subjects.Methods: MS patients starting NZ (MS-NZ), MS controls with stable interferon beta therapy (MS-C) and healthy control subjects (HC) were evaluated twice with one year interval, using a cognitive test battery covering six cognitive domains. The effects of NZ on levels of self-reported depression, fatigue, daytime sleepiness and perceived health were also examined.Results: MS patients (MS-NZ and MS-C) had significantly lower baseline cognitive performance compared to HC (global score, p=0.002), but there were no significant differences between MS-NZ and MS-C. At follow-up, both MS-NZ and MS-C had improved significantly in four and five cognitive domains, respectively, and in global score (p=0.013 and p<0.001, respectively). HC improved significantly in three cognitive domains but not in global score. A regression analysis including baseline cognitive z-score and z-score change showed that participants with lower baseline scores had a significantly greater improvement, compared to those with better initial performance (p=0.021). There were no significant changes in depression, fatigue, daytime sleepiness or perceived health in MS-NZ or MS-C.Conclusions: Initiation of NZ therapy did not result in true cognitive improvement over one year. Presumably, the increased test performance in both MS groups was artificial and due to retest effects that were stronger in patients with lower baseline performance. Adequate control groups are essential when evaluating cognitive functioning in intervention trials among RRMS patients.
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| 49. |
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| 50. |
- Tedeholm, Helen, 1978, et al.
(författare)
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Effectiveness of first generation disease-modifying therapy to prevent conversion to secondary progressive multiple sclerosis.
- 2022
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Ingår i: Multiple Sclerosis and Related Disorders. - : Elsevier. - 2211-0348 .- 2211-0356. ; 68
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The use of disease-modifying therapies (DMTs) in multiple sclerosis (MS) has been associated with reduced relapse rates and accumulation of disability. However, studies examining impact of DMT on risk of transition to secondary progressive MS (SPMS) leveraging population-based nationwide data are still rare. Here, we determine the population incidence of conversion to SPMS using two consecutive nation-wide cohorts, one immediately before and one after the introduction of DMT in Sweden.METHODS: We included two consecutive population cohorts of relapsing-remitting MS (RRMS) from the Swedish national MS register for the periods 1975-1994 (n = 2161), before DMT availability, and 1995-2011 (n = 3510), in which DMTs, mainly first generation DMT (injectables), became available and eventually were used by 70% of patients. We explored the risk of transition to SPMS as a calendar year function encompassing the two cohorts. In addition, we determined the incidence of transition to SPMS through age strata below and above 50 years in untreated and treated patient subgroups.RESULTS: The risk of conversion to SPMS (adjusted for current age, current time since onset, calendar year and sex) was significantly lower in the second compared with the first population cohort (hazard ratio 0.58; CI 0.48, 0.70). The risk of SPMS conversion per calendar year decreased by 2.6% annually (p < 0.001) after 1995. The risk of SPMS conversion increased with age until age 50. Thereafter, it was unchanged or decreased among those with early MS onset age (<35 years), but continued to increase with onset at higher age, with similar trends in treated and untreated subgroups.CONCLUSION: The incidence of SPMS conversion significantly decreased at the population level after introduction of first generation DMTs by 1995. DMT efficiency was confirmed by a downward turn of the annual trajectory of the risk of SPMS conversion after 1995. An onset age determined pattern of variable SPMS incidence in higher age appeared in both treated and untreated strata. While first generation DMT delayed conversion to SPMS, their long-term effect was only moderate.
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