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  • 1.
    Alping, Peter
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Piehl, Fredrik
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Academic Specialist Center, Stockholm Health Services, Stockholm, Sweden; Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
    Langer-Gould, Annette
    Clinical and Translational Neuroscience, Southern Clinical and Translational Neuroscience, Southern California Permanente Medical Group, Kaiser Permanente, Pasadena CA, USA.
    Frisell, Thomas
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Burman, Joachim
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Fink, Katharina
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Fogdell-Hahn, Anna
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Center for Health and Medical Psychology.
    Hillert, Jan
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Kockum, Ingrid
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Lycke, Jan
    Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Gothenburg, Sweden.
    Nilsson, Petra
    Department of Clinical Sciences/Neurology, Lund University, Lund, Sweden.
    Olsson, Tomas
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Salzer, Jonatan
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå.
    Svenningsson, Anders
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Virtanen, Suvi
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Vrethem, Magnus
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Validation of the Swedish Multiple Sclerosis Register Further Improving a Resource for Pharmacoepidemiologic Evaluations2019Ingår i: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 30, nr 2, s. 230-233Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The Swedish Multiple Sclerosis Register is a national register monitoring treatment and clinical course for all Swedish multiple sclerosis (MS) patients, with high coverage and close integration with the clinic. Despite its great value for epidemiologic research, it has not previously been validated. In this brief report, we summarize a large validation of >3,000 patients in the register using clinical chart review in the context of the COMBAT-MS study. While further improving the data quality for a central cohort of patients available for future epidemiologic research, this study also allowed us to estimate the accuracy and completeness of the register data.

  • 2.
    Axelsson, Markus
    et al.
    University of Gothenburg, Gothenburg, Sweden .
    Malmeström, Clas
    University of Gothenburg, Gothenburg, Sweden .
    Gunnarsson, Martin
    Örebro universitet, Institutionen för läkarutbildning. Region Örebro län.
    Zetterberg, Henrik
    University of Gothenburg, Mölndal, Sweden; Institute of Neurology, The University College London (UCL), London, UK.
    Sundstrom, Peter
    Umeå University, Umeå, Sweden .
    Lycke, Jan
    University of Gothenburg, Gothenburg, Sweden .
    Svenningsson, Anders
    Umeå University, Umeå, Sweden .
    Immunosuppressive therapy reduces axonal damage in progressive multiple sclerosis2014Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, nr 1, s. 43-50Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: In progressive multiple sclerosis (PMS), disease-modifying therapies have not been shown to reduce disability progression.

    Objective: The impact from immunosuppressive therapy in PMS was explored by analyzing cerebrospinal fluid (CSF) biomarkers of axonal damage (neurofilament light protein, NFL), astrogliosis (glial fibrillary acidic protein, GFAP), and B-cell regulation (CXCL13).

    Methods: CSF was obtained from 35 patients with PMS before and after 12-24 months of mitoxantrone (n=30) or rituximab (n=5) treatment, and from 14 age-matched healthy control subjects. The levels of NFL, GFAP, and CXCL13 were determined by immunoassays.

    Results: The mean NFL level decreased by 51% (1781 ng/l, SD 2018 vs. 874 ng/l, SD 694, p=0.007), the mean CXCL13 reduction was 55% (9.71 pg/ml, SD 16.08, vs. 4.37 pg/ml, SD 1.94, p=0.008), while GFAP levels remained unaffected. Subgroup analysis showed that the NFL reduction was confined to previously untreated patients (n=20) and patients with Gd-enhancing lesions on magnetic resonance imaging (n=12) prior to study baseline.

    Conclusions: Our data imply that 12-24 months of immunosuppressive therapy reduces axonal damage in PMS, particularly in patients with ongoing disease activity. Determination of NFL levels in CSF is a potential surrogate marker for treatment efficacy and as endpoint in phase II trials of MS.

  • 3.
    Biström, M.
    et al.
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Andersen, O.
    Department of Clinical Neuroscience, Institution of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Alonso-Magdalena, L.
    Department of Neurology, Skåne University Hospital, Malmö, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Vrethem, M.
    Department of Neurology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Hultdin, J.
    Department of Medical Biosciences, Clinical Chemistry, Umeå University, Umeå, Sweden.
    Sundström, P.
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    High serum concentrations of vitamin D may protect against multiple sclerosis2018Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, nr Suppl. 2, s. 1001-1002Artikel i tidskrift (Övrigt vetenskapligt)
  • 4.
    Biström, M.
    et al.
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Hultdin, J.
    Department of Medical Biosciences, Clinical Chemistry, Umeå University, Umeå, Sweden.
    Andersen, O.
    Department of Clinical Neuroscience, Institution of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg.
    Alonso-Magdalena, L.
    Department of Neurology, Skåne University Hospital, Malmö, sweden.
    Jons, D.
    Department of Clinical Neuroscience, Institution of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Vrethem, M.
    Department of Neurology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Sundström, P.
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Leptin levels are associated with multiple sclerosis risk2019Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, nr Suppl. 2, s. 904-904Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Introduction: One environmental factor that in the last decade repeatedly has been linked to increased risk of developing multiple sclerosis (MS) is overweight, including obesity, early in life. The incidence of both MS and overweight are increasing, making elucidation of this connection important. The adipokine leptin is strongly correlated to both body mass index and total fat mass and the peptide hormone insulin is associated with obesity and type 2 diabetes, making leptin and insulin suitable biomarkers to investigate the connection between overweight and MS.

    Objectives: To determine if leptin or insulin are risk factors for developing relapsing MS.

    Aims: To further the understanding of how overweight influence MS risk.

    Methods: In this case-control study, we compared concentrations of leptin and insulin in 649 individuals that later developed relapsing-remitting MS with 649 matched controls. Cases were matched for biobank, sex, date of sampling and age with decreasing priority. Only prospectively collected samples from individuals below the age of 40 were included in the study. Conditional logistic regression was performed on log10 transformed and z-scored values for the entire group, separately for men and women and divided into age groups.

    Results: A 1-unit leptin z-score increase was associated with increased risk of MS in individuals below 20 years of age (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.1–1.9) and for 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. No statistically significant association was found between insulin levels and MS risk.

    Conclusions: We show that the pro-inflammatory adipokine leptin is a risk factor for MS among young individuals. The age dependent relationship between leptin and MS risk in women - for whom leptin levels are several-fold higher than in men - suggests a possible role for leptin as being the link between MS risk and being overweight early in life.

  • 5.
    Bridel, Claire
    et al.
    Neurochemistry Laboratory, Department of Clinical Chemistry, VU University Medical Centre, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Weiss, Edward J.
    UCL Institute of Neurology, London, England.
    Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology: A Systematic Review and Meta-analysis2019Ingår i: JAMA Neurology, ISSN 2168-6149, E-ISSN 2168-6157, Vol. 76, nr 9, s. 1035-1048Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Key Points: QuestionHow do levels of neurofilament light in cerebrospinal fluid (cNfL) compare between neurological conditions and with healthy controls?

    Findings: Among 10 059 individuals in this systematic review and meta-analysis, cNfL was elevated in most neurological conditions compared with healthy controls, and the magnitude of the increase varies extensively. Although cNfL overlaps between most clinically similar conditions, its distribution did not overlap in frontotemporal dementia and other dementias or in Parkinson disease and atypical parkinsonian syndromes.

    Meaning: The cNfL is a marker of neuronal damage and may be useful to differentiate some clinically similar conditions, such as frontotemporal dementia from Alzheimer disease and Parkinson disease from atypical parkinsonian syndromes.

    This systematic review and meta-analysis assesses the associations of age, sex, and diagnosis with neurofilament light in cerebrospinal fluid and evaluates its potential in discriminating clinically similar conditions.

    Importance: Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.

    Objectives: To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.

    Data Sources: PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.

    Study Selection: Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.

    Data Extraction and Synthesis: Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.

    Main Outcome and Measure: The cNfL levels adjusted for age and sex across diagnoses.

    Results: Data were collected for 10059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n=2795), dementias and predementia stages (n=4284), parkinsonian disorders (n=984), and HC (n=1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.

    Conclusions and Relevance: These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.

  • 6.
    Burman, Joachim
    et al.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden; Department of Neurology, Uppsala University Hospital, Uppsala, Sweden .
    Iacobaeus, Ellen
    Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institute Solna, Center for Molecular Medicine, Stockholm, Sweden.
    Svenningsson, Anders
    Department of Pharmacology and Clinical Neuroscience, Umeå University and University Hospital of Northern Sweden, Umeå, Sweden .
    Lycke, Jan
    Department of Neurology, Institute of Neuroscience and Physiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för läkarutbildning. Department of Neurology, Örebro University Hospital, Örebro, Sweden .
    Nilsson, Petra
    Department of Neurology, Skåne University Hospital Lund, Lund, Sweden.
    Vrethem, Magnus
    Neurology and Clinical Neurophysiology, Faculty of Health Sciences, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Neurology and Neurophysiology, County Council of Östergötland, Linköping, Sweden .
    Fredrikson, Sten
    Department of Clinical Neuroscience, Karolinska Institute Huddinge, Stockholm, Sweden .
    Martin, Claes
    Neurology Unit, Division of Internal Medicine, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden .
    Sandstedt, Anna
    Department of Hematology, Linköping University Hospital, Linköping, Sweden .
    Uggla, Bertil
    Örebro universitet, Institutionen för läkarutbildning. Region Örebro län. Division of Hematology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Lenhoff, Stig
    Department of Hematology and Coagulation, Skåne University Hospital, Lund, Sweden .
    Johansson, Jan-Erik
    Department of Hematology and Coagulation, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Isaksson, Cecilia
    Department of Radiosciences, Umeå University, Umeå, Sweden .
    Hägglund, Hans
    Division of Hematology, Department of Medical Science, Uppsala University Hospital, Uppsala, Sweden.
    Carlson, Kristina
    Division of Hematology, Department of Medical Science, Uppsala University Hospital, Uppsala, Sweden.
    Fagius, Jan
    Department of Neuroscience, Uppsala University, Uppsala, Sweden; Department of Neurology, Uppsala University Hospital, Uppsala, Sweden .
    Autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: the Swedish experience2014Ingår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 85, nr 10, s. 1116-1121Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Autologous haematopoietic stem cell transplantation (HSCT) is a viable option for treatment of aggressive multiple sclerosis (MS). No randomised controlled trial has been performed, and thus, experiences from systematic and sustained follow-up of treated patients constitute important information about safety and efficacy. In this observational study, we describe the characteristics and outcome of the Swedish patients treated with HSCT for MS.

    Methods: Neurologists from the major hospitals in Sweden filled out a follow-up form with prospectively collected data. Fifty-two patients were identified in total; 48 were included in the study and evaluated for safety and side effects; 41 patients had at least 1 year of follow-up and were further analysed for clinical and radiological outcome. In this cohort, 34 patients (83%) had relapsing-remitting MS, and mean follow-up time was 47 months.

    Results: At 5 years, relapse-free survival was 87%; MRI event-free survival 85%; expanded disability status scale (EDSS) score progression-free survival 77%; and disease-free survival (no relapses, no new MRI lesions and no EDSS progression) 68%. Presence of gadolinium-enhancing lesions prior to HSCT was associated with a favourable outcome (disease-free survival 79% vs 46%, p=0.028). There was no mortality. The most common long-term side effects were herpes zoster reactivation (15%) and thyroid disease (8.4%).

    Conclusions: HSCT is a very effective treatment of inflammatory active MS and can be performed with a high degree of safety at experienced centres.

  • 7.
    Carling, Anna
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. University Healthcare Research Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Physiotherapy, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Forsberg, Anette
    Örebro universitet, Institutionen för hälsovetenskaper. University Healthcare Research Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Nilsagård, Ylva
    Örebro universitet, Institutionen för hälsovetenskaper. Region Örebro län. University Healthcare Research Centre.
    CoDuSe group exercise programme improves balance and reduces falls in people with multiple sclerosis: A multi-centre, randomized, controlled pilot study2017Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 23, nr 10, s. 1394-1404Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Imbalance leading to falls is common in people with multiple sclerosis (PwMS).

    Objective: To evaluate the effects of a balance group exercise programme (CoDuSe) on balance and walking in PwMS (Expanded Disability Status Scale, 4.0-7.5).

    Methods: A multi-centre, randomized, controlled single-blinded pilot study with random allocation to early or late start of exercise, with the latter group serving as control group for the physical function measures. In total, 14 supervised 60-minute exercise sessions were delivered over 7 weeks. Pretest-posttest analyses were conducted for self-reported near falls and falls in the group starting late. Primary outcome was Berg Balance Scale (BBS). A total of 51 participants were initially enrolled; three were lost to follow-up.

    Results: Post-intervention, the exercise group showed statistically significant improvement (p = 0.015) in BBS and borderline significant improvement in MS Walking Scale (p = 0.051), both with large effect sizes (3.66; -2.89). No other significant differences were found between groups. In the group starting late, numbers of falls and near falls were statistically significantly reduced after exercise compared to before (p < 0.001; p < 0.004).

    Conclusion: This pilot study suggests that the CoDuSe exercise improved balance and reduced perceived walking limitations, compared to no exercise. The intervention reduced falls and near falls frequency.

  • 8.
    de Flon, Pierre
    et al.
    Department of Pharmacology and Clinical Neuroscience, Unit of Neurology, Östersund, Umeå University, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Laurell, Katarina
    Department of Pharmacology and Clinical Neuroscience, Unit of Neurology, Östersund, Umeå University, Umeå, Sweden.
    Söderström, Lars
    Unit of Research, Education and Development, Region Jämtland Härjedalen, Sweden.
    Birgander, Richard
    Department of Radiation Sciences, Diagnostic Radiology, Umeå University, Umeå, Sweden.
    Lindqvist, Thomas
    Department of Radiation Sciences, Diagnostic Radiology, Umeå University, Umeå, Sweden.
    Krauss, Wolfgang
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Radiology.
    Dring, Ann
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Bergman, Joakim
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Sundström, Peter
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Svenningsson, Anders
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden; Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Reduced inflammation in relapsing-remitting multiple sclerosis after therapy switch to rituximab2016Ingår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 87, nr 2, s. 141-147Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To describe the effects of switching treatment from ongoing first-line injectable therapies to rituximab on inflammatory activity measured by MRI and levels of CSF neurofilament light chain (CSF-NFL) in a cohort of patients with clinically stable relapsing-remitting multiple sclerosis (RRMS).

    Method: Seventy-five patients with clinically stable RRMS treated with the first-line injectables interferon-β (IFN-β) and glatiramer acetate (GA) at 3 Swedish centers were switched to rituximab in this open-label phase II multicenter study. After a run-in period of 3 months, 2 IV doses of 1,000 mg rituximab were given 2 weeks apart followed by repeated clinical assessment, MRI, and CSF-NFL for 24 months.

    Results: The mean cumulated number of gadolinium-enhancing lesions per patient at months 3 and 6 after treatment shift to rituximab was reduced compared to the run-in period (0.028 vs 0.36, p = 0.029). During the first year after treatment shift, the mean number of new or enlarged T2 lesions per patient was reduced (0.01 vs 0.28, p = 0.004) and mean CSF-NFL levels were reduced by 21% (p = 0.01).

    Conclusions: For patients with RRMS, a treatment switch from IFN or GA to rituximab is associated with reduced inflammatory activity measured by MRI and CSF-NFL.

    Classification of evidence: This study provides Class IV evidence that rituximab has an equal or superior effect in reducing inflammatory activity in RRMS measured by MRI and CSF-NFL compared to first-line injectables during the first year after treatment shift.

  • 9.
    de Flon, Pierre
    et al.
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Laurell, Katarina
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Sundström, Peter
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Blennow, Kaj
    Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
    Söderström, Lars
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Zetterberg, Henrik
    Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK; UK Dementia Research Institute at UCL, London, UK.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Svenningsson, Anders
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden; Department of Clinical Sciences, Karolinska Institute Danderyd Hospital, Stockholm, Sweden.
    Comparison of plasma and cerebrospinal fluid neurofilament light in a multiple sclerosis trial2019Ingår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 139, nr 5, s. 462-468Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: The main objective of this study was to evaluate the axonal component neurofilament light protein (NFL) in plasma and cerebrospinal fluid (CSF) as an outcome measure in a clinical trial on disease-modifying treatments in multiple sclerosis.

    MATERIALS & METHODS: Seventy-five patients with clinically stable relapsing-remitting multiple sclerosis (RRMS) participating in the clinical trial "Switch-To RItuXimab in MS" (STRIX-MS) were switched to rituximab from first-line injectable therapy and then followed for two years. Thirty patients from the extension trial (STRIX-MS extension), accepting repeated lumbar punctures, were followed for an additional three years. Plasma and CSF samples were collected yearly during the follow-up. NFL concentration in plasma was measured by an in-house NF-light assay on the Simoa platform with a Homebrew kit. NFL concentration in CSF was measured by sandwich ELISA.

    RESULTS: The mean levels of NFL, in both CSF and plasma, were low. The reduction of CSF-NFL was 25% during the first year of follow-up (from a mean of 471 (SD 393) to 354 (SD 174) pg/mL; p=0.006) and was statistically significant. The corresponding reduction in plasma-NFL was 18% (from 9.73 (SD 7.04) to 7.94 (SD 3.10) pg/mL; p=0.055) and did not reach statistical significance.

    CONCLUSION: This study indicates that NFL in plasma is less sensitive as an endpoint in group comparisons than NFL in CSF. Given that plasma NFL is far easier to access, it is a promising and awaited method but further studies are needed to optimise the use in clinical trials.

  • 10.
    de Flon, Pierre
    et al.
    Department of Neurology, Östersund Hospital, Östersund, Sweden; Neurology Unit, Department of Pharmacology and Clinical Neuroscience, Umeå University, Östersund, Sweden.
    Laurell, Katarina
    Neurology Unit, Department of Pharmacology and Clinical Neuroscience, Umeå University, Östersund, Sweden.
    Söderström, Lars
    Unit of Research, Education and Development, Östersund Hospital, Region Jämtland Härjedalen, Östersund, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Svenningsson, Anders
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden; Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden; Karolinska Institutet, Stockholm, Sweden.
    Improved treatment satisfaction after switching therapy to rituximab in relapsing-remitting MS2017Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 23, nr 9, s. 1249-1257Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: New disease-modifying treatment strategies in multiple sclerosis offer possibilities for individualised treatment. In this study, we evaluated patient-reported outcome measures before and after a switch in therapy from first-line injectable treatments to rituximab.

    Method: A total of 75 patients with clinically stable relapsing-remitting multiple sclerosis (RRMS) receiving ongoing first-line injectable treatment at three Swedish centres had their treatment switched to rituximab in this open-label phase II multicentre study. Assessment of treatment satisfaction, patient-perceived impact of the disease on daily life, fatigue, cognitive symptoms and disease progression was performed 3 months before and at the time of the treatment shift and then for a subsequent 2-year period.

    Results: The overall treatment satisfaction rating improved significantly from a mean of 4.8 (scale range: 1-7), while on injectable therapies, to a mean of 6.3 after 1 year of rituximab treatment (p < 0.001). This improvement was sustained after 2 years. There was no significant change in scores for patient-perceived impact of disease, fatigue or disease progression.

    Conclusion: A shift in therapy from first-line injectables to rituximab in a cohort of clinically stable RRMS patients was followed by improved treatment satisfaction. This is clinically relevant as it may influence long-term adherence to immunomodulating therapy.

  • 11.
    de Flon, Pierre
    et al.
    Dept of Pharmacology and Clinical Neuroscience, Neurology, Umeå University, Umeå, Sweden.
    Söderström, Lars
    Unit of Research, Education and Development, Östersund Hospital, Region Jaämtland Härjedalen, Östersund, Sweden.
    Laurell, Katarina
    Dept of Pharmacology and Clinical Neuroscience, Neurology, Umeå University, Umeå, Sweden.
    Dring, Ann
    Dept of Pharmacology and Clinical Neuroscience, Neurology, Umeå University, Umeå, Sweden.
    Sundström, Peter
    Dept of Pharmacology and Clinical Neuroscience, Neurology, Umeå University, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Dept of Neurology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Svenningsson, Anders
    Dept of Pharmacology and Clinical Neuroscience, Neurology, Umeå University, Umeå, Sweden; Dept of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Immunological profile in cerebrospinal fluid of patients with multiple sclerosis after treatment switch to rituximab and compared with healthy controls2018Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 2, artikel-id e0192516Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To investigate changes in the cerebrospinal fluid (CSF) immunological profile after treatment switch from first-line injectables to rituximab in patients with relapsing-remitting MS (RRMS), and to compare the profile in MS patients with healthy controls (HC).

    Method: Cerebrospinal fluid from 70 patients with clinically stable RRMS and 55 HC was analysed by a multiplex electrochemiluminescence method for a broad panel of cytokines and immunoactive substances before, and over a two-year period after, treatment switch to rituximab. After quality assessment of data, using a predefined algorithm, 14 analytes were included in the final analysis.

    Results: Ten of the 14 analytes differed significantly in MS patients compared with HC at baseline. Levels of IP-10 (CXCL10), IL-12/23p40, IL-6, sVCAM1, IL-15, sICAM1 and IL-8 (CXCL8) decreased significantly after treatment switch to rituximab. The cytokines IP-10 and IL-12/IL-23p40 displayed the largest difference versus HC at baseline and also the largest relative reduction after therapy switch to rituximab.

    Conclusion: We found significant changes in the immunological profile after therapy switch to rituximab in RRMS in the direction towards the values of HC. IP-10 and IL12/IL-23p40 deserve further studies as part of the immunopathogenesis of MS as well as for the mode of action of rituximab in MS.

  • 12.
    Demirbüker, S. Safer
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Kågström, S.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Fält, A.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Berglund, A.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hillert, J.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, P.
    Department of Neurology, Lund University, Lund, Sweden.
    Dahle, C.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Svenningsson, A.
    Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
    Lycke, J.
    Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Gothenburg, Sweden.
    Landtblom, A. -M
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Burman, J.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Sundström, P.
    Department of Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Martin, C.
    Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Piehl, F.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Olsson, T.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    A Swedish nationwide pharmaco-epidemiological and genetic study of the long-term safety and effectiveness of dimethyl fumarate (IMSE 5)2018Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, nr Suppl. 2, s. 701-702Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Dimethyl fumarate (DMF) is an oral therapy for relapsing-remitting multiple sclerosis (RRMS), which has been included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology 5” (IMSE 5) in order to monitor and determine the long-term safety and effectiveness in a real-world setting.

    Objectives: To follow-up the long-term safety and effectiveness of DMF in a real-world setting.

    Methods: MS patients are registered into the nationwide Swedish Neuro Registry (NeuroReg) in Sweden. The IMSE 5 study obtains descriptive data of adverse events (AEs), Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - Five Dimensions Test (EQ-5D) and Visual Analog Scale (VAS) from NeuroReg. Drug survival was measured using the Kaplan-Meier curve and effectiveness measures were assessed using the Wilcoxon Signed Rank Test.

    Results: 2010 DMF-treated patients have been included in the IMSE 5 study between March 2014 and April 2018. 73 % were female and the mean age at treatment start was 40.6 years. The mean treatment duration was 22.3 months. 92 % of the patients had RRMS with 2 % missing data on MS phenotype. Most patients switched from interferon and glaimer acetat (41 %) and 24 % of the patients were treatment naïve (13 % were missing data on prior treatment). The overall one year drug survival was 74 % and 889 patients terminated their treatment at some point. Most patients (39 %) switched to rituximab (15 % have no new treatment registered). The most common reason for discontinuation was AEs (53 %) and lack of effect (29 %). 227 (11 %) patients have continued treatment for ≥36 months. In patients treated with DMF continuously for ≥24 months (n=918), significant improvements in mean values at 24 months of treatment compared to mean baseline values have been noted for EDSS (1.9 ± 1.6 to 1.6 ± 1.6, n=196); MSSS (2.5 ± 2.4 to 2.0 ± 2.0, n=145); SDMT (52.6 ± 11.0 to 53.8 ± 11.7, n=315); MSIS-29 Psychological Subscale (26.3 ± 22.8 to 21.8 ± 20.6, n=337); and EQ-5D (0.76 ± 0.23 to 0.81 ± 0.20, n=284).

    Conclusions: NeuroReg proves to function well as a post-marketing drug surveillance platform, providing data regarding drug effectiveness and AEs. A longer follow-up period is needed to assess the real-world effectiveness and safety of DMF.

  • 13.
    Demirbüker, S. Safer
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Kågström, S.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Fält, A.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hillert, J.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, P.
    Department of Neurology, Lund University, Lund, Sweden.
    Dahle, C.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Svenningsson, A.
    Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
    Lycke, J.
    Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Gothenburg, Sweden.
    Landtblom, A. -M
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Burman, J.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Sundström, P.
    Department of Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Martin, C.
    Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Piehl, F.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Olsson, T.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of teriflunomid (IMSE 4)2018Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, nr Suppl. 2, s. 922-923Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Teriflunomid (TFM) is an oral therapy for relapsing-remitting multiple sclerosis (RRMS), which has been included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology 4” (IMSE 4) in order to surveille and determine the long-term safety and effectiveness in a real-world setting.

    Objectives: To follow-up the long-term safety and effectiveness of TFM in a real-world setting.

    Methods: MS patients are registered into the nationwide Swedish Neuro Registry (NeuroReg) in Sweden. The IMSE 4 study obtains descriptive data of adverse events (AEs), Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - Five Dimensions Test (EQ-5D) and Visual Analog Scale (VAS) from NeuroReg. Drug survival was measured using the Kaplan-Meier curve.

    Results: 481 TFM-treated patients have been included in the IMSE 4 study between March 2014 and April 2018. 70 % were female and the mean age at treatment start was 45.8 years. The mean treatment duration was 20.5 months. 89 % of the patients had RRMS with 3 % missing data on MS phenotype. Most patients switched from interferon and glatimer acetat (37 %) and 14 % of the patients were treatment naïve before starting TFM. The overall one year drug survival rate was 81 % and the overall two year drug survival rate was 41 %. 168 (35 %) patients terminated their treatment at some point, of which 33 % started rituximab treatment and 22 % have no new treatment registered. The most common reasons for discontinuation were AEs (49 %) and lack of effect (40 %). 318 patients have been continuously treated with TFM for ≥12 months and mean baseline values compared to val-ues at 12 months have been noted for EDSS (2.0 ± 1.5 to 2.2 ± 1.5, n=141); MSSS (2.6 ± 2.2 to 2.9 ± 2.3, n=126); SDMT (50.8 ± 10.5 to 50.8 ± 10.7, n=165); MSIS-29 Physiological subscale (20.2 ± 19.3 to 19.7 ± 20.0, n=181); MSIS-29 Psychological subscale (28.1 ± 22.2 to 23.7 ± 21.7, n=181); EQ-5D (0.74 ± 0.24 to 0.73 ± 0.26, n=154); and VAS (70.0 ± 20.8 to 70.8 ± 19.6, n=150).

    Conclusions: NeuroReg proves to function well as a post-marketing drug surveillance platform, providing data regarding drug effectiveness and AEs. However, a longer follow-up period is needed to assess the real-world effectiveness and safety of TMF.

  • 14.
    Forsberg, L.
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Kågström, S.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Fält, A.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Berglund, A.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hillert, J.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, P.
    Department of Neurology, Lund University, Lund, Sweden.
    Dahle, C.
    Department of Clinical and Experimental Medicine, Linköping University, Sweden.
    Svenningsson, A.
    Department of Clinical Science, Danderyd Hospital, Stockholm, Sweden.
    Lycke, J.
    Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Gothenburg, Sweden.
    Landtblom, A. -M
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Burman, J.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Martin, C.
    Department of Clinical Science, Danderyd Hospital, Stockholm, Sweden.
    Sundström, P.
    Department of Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Piehl, F.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Olsson, T.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Clinical effectiveness of dimethyl fumarate with focus on patients treated at least 36 months - a Swedish nationwide study of the long-term effectiveness and safety of dimethyl fumarate (IMSE5)2019Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, nr Suppl. 2, s. 316-317Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Dimethyl fumarate (DMF) is an oral therapy for relapsing-remitting multiple sclerosis (RRMS). DMF is included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology” (IMSE).

    Objective: To assess the effectiveness and safety of DMF with focus on patients treated at least 36 months in the IMSE study.

    Methods: Descriptive data of Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - 5 Dimensions Test (EQ-5D), Visual Analog Scale (VAS) and Adverse Events (AEs) is obtained from the nationwide Swedish Neuro Registry (NeuroReg). Effectiveness measures were assessed using the Wilcoxon Signed Rank Test and drug survival using the Kaplan-Meier curve.

    Results: 2229 DMF-treated patients were included since March 2014 with a one- and two-year drug survival rate of 73% and 59%. The main reasons for discontinuation were AEs (51%) and lack of effect (29%). 77 AEs were reported to the Swedish Medical Products Agency of which 20 were serious. There were 6 fatal cases of which 4 were confirmed as unrelated to DMF and 2 were still under investigation.865 patients had continuous treatment for at least 36 months. This cohort had a mean age of 42 years and a mean treatment duration of 44 months. The majority had switched from interferon and glatiramer acetate (IFN&GA) (50%) or were treatment naïve (TN) (22%). Significant improvements in mean values at 36 months of treatment compared to baseline were noted for EDSS, MSSS, SDMT, MSIS-29 Psychological and EQ-5D. When TN patients were solely assessed improvements were noted for EDSS, MSSS, SDMT, MSIS-29 Physical and Psychological and EQ-5D. Treatment experienced patients displayed significant improvements only for MSSS and EQ-5D. Patients previously treated with IFN&GA also improved only in MSSS and EQ-5D. TN patients had a mean duration from diagnosis to treatment start of 6 months compared to 83 months for IFN&GA patients and 105 months for the remaining cohort.

    Conclusions: DMF demonstrates clinical improvements in patients treated ⩾ 36 months, most pronounced in TN patients. However; the tolerability of DMF was reduced since 41% interrupted treatment during the first 24 months of therapy. Continued follow up is needed to assess the effectiveness and safety of DMF over longer time periods in a real world setting.

  • 15.
    Forsberg, L.
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Kågström, S.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Fält, A.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hillert, J.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, P.
    Department of Neurology, Lund University, Lund, Sweden.
    Dahle, C.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Svenningsson, A.
    Department of Clinical Science, Danderyd Hospital, Stockholm, Sweden.
    Lycke, J.
    Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Gothenburg, Sweden.
    Landtblom, A. -M
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Burman, J.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Martin, C.
    Department of Clinical Science, Danderyd Hospital, Stockholm, Sweden.
    Sundström, P.
    Department of Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Piehl, F.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Olsson, T.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    A Swedish Nationwide study of the long-term effectiveness and safety of teriflunomid based on data from the Swedish "Immunomodulation and Multiple Sclerosis Epidemiology" Study (IMSE 4)2019Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, nr Suppl. 2, s. 316-316Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Teriflunomid (TFM) is a newly approved oral therapy for relapsing-remitting multiple sclerosis (RRMS), which has been included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology” (IMSE) in order to track the long-term safety and effectiveness in a real-world setting.

    Objectives: To track the long-term safety and effectiveness of TFM in a real-world setting.

    Methods: A large majority of MS patients are registered into the nationwide Swedish Neuro Registry (NeuroReg). The IMSE 4 study obtains descriptive data of adverse events (AEs), Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - Five Dimensions Test (EQ-5D) and Visual Analog Scale (VAS) from NeuroReg. Drug survival was measured using the Kaplan-Meier curve.

    Results: A total of 559 TFM-treated patients had been included in the IMSE 4 study from March 2014 to March 2019. 71 % were female and the mean age at treatment start was 46 years. The mean treatment duration was 23 months and 89 % of the patients had RRMS (9 % missing data on MS phenotype). Most patients switched from interferon/glatiramer acetate (36 %) and 16 % of the patients were treatment naïve before starting TFM. The overall one-year drug survival rate was 74 % and the overall two-year drug survival rate was 58 %. 232 (42 %) patients had terminated their treatment at some point, of which 46 % started rituximab treatment and 12 % had no new treatment registered. The most common reasons for discontinuation were AEs (41 %) and lack of effect (39 %). 229 patients had been continuously treated with TFM for ⩾24 months and significant changes in mean baseline values compared to values at 24 months were noted for EDSS (1.9 ± 1.5 to 2.1 ± 1.6, n=66) and SDMT (50.3 ± 10.5 to 52.3 ± 13.0, n=88). A total of 34 AEs were reported to the Swedish Medical Products Agency of which 9 events were classified as serious, none fatal.

    Conclusions: NeuroReg proves to function well as a post-marketing drug surveillance platform, providing data regarding drug effectiveness and AEs. Patients starting TMF are older at treat-ment start than most other DMTs, which may explain the lack of improvement in EDSS scores. Still, a relatively high proportion switched due to lack of effect. A longer follow-up period is needed to assess the real-world effectiveness and safety of TMF.

  • 16.
    Fält, A.
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Kågström, S.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Demirbuker, S. Safer
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hillert, J.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, P.
    Department of Neurology, Lund University, Lund, Sweden.
    Dahle, C.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Svenningsson, A.
    Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
    Lycke, J.
    Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Gothenburg, Sweden.
    Landtblom, A. -M
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Burman, J.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Martin, C.
    Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
    Sundström, P.
    Department of Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Piehl, F.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Olsson, T.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of alemtuzumab (IMSE 3)2018Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, nr Suppl. 2, s. 706-707Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Alemtuzumab (ALZ) is a modulatory drug for patients with relapsing-remitting multiple sclerosis (RRMS). Post-marketing surveillance is important to assess the long term safety and effectiveness in a real-world setting. ALZ has therefore been included into the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology Study 3” (IMSE 3) upon launch in Sweden (March 2014).

    Objective: To follow up the effectiveness and long-term safety of ALZ in a real-world setting.

    Methods: Swedish MS patients are registered into the nationwide Swedish Neuro Registry (NeuroReg). IMSE 3 includes patients starting ALZ treatment. Adverse events (AEs) and clinical meas-ures; Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - 5 Dimension Test (EQ-5D) and Visual Analogue Scale (VAS) are obtained from NeuroReg. The Wilcoxon signed-rank test was used to assess changes in effectiveness.

    Results: 110 patients (60% female; 95% RRMS) have been included in IMSE 3 between March 2014 and April 2018. Mean age at treatment start was 34 years and mean treatment duration was 28 months. Most patients (40%) switched from natalizumab and 14% were treatment naïve. 103 patients were currently treated with ALZ at cut-off date and 97 patients had been treated for at least 12 months. Seven patients had discontinued ALZ treatment, of which five patients switched to another disease modifying therapy, one patient died in association with the first ALZ treatment cycle due to fulminant viral hepatitis and one patient had no treatment registered after ALZ discontinuation. In total, 20 AEs were reported to the Swedish Medical Products Agency; 13 events were classified as non-serious. In patients treated at least 12 months significant improvements were seen for EDSS (2.0±1.4 to 1.6±1.3, n=67), MSSS (3.4±2.6 to 2.6±2.3, n=58), MSIS-29 Physical (22.9±21.0 to 17.5±18.0, n=83), VAS (66.9±22.0 to 73.7±18.5, n=68) and EQ-5D (0.7±0.3 to 0.8±0.3, n=74). MSIS-29 Psychological and SDMT did not improve significantly.

    Conclusions: NeuroReg functions well as a post-marketing drug surveillance platform, providing data regarding drug effectiveness and AEs. A longer follow-up period is needed to evaluate the real-world effectiveness and safety of ALZ.

  • 17.
    Fält, A.
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Kågström, S.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Demirbüker, S. Safer
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hillert, J.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, P.
    Department of Neurology, Lund University, Lund, Sweden.
    Dahle, C.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Svenningsson, A.
    Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
    Lycke, J.
    Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Gothenburg, Sweden.
    Landtblom, A. -M
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Burman, J.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Martin, C.
    Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
    Sundström, P.
    Department of Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Piehl, F.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Olsson, T.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of fingolimod (IMSE 2)2018Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, nr Suppl. 2, s. 696-697Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Fingolimod (FGL) is an oral therapy for patients with relapsing-remitting multiple sclerosis (RRMS) and the efficacy has been shown in phase II and III studies. However; long-term surveillance and safety is important, therefore FGL is included in the Swedish “Immunomodulation and Multiple Sclerosis Epidemiology Study 2” (IMSE 2).

    Objective: To follow up the effectiveness and long-term safety of FGL in a real-world setting.

    Methods: Swedish MS patients are registered into the nationwide Swedish Neuro Registry (NeuroReg). IMSE 2 includes data of adverse events (AEs) and clinical measures; Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - 5 Dimension Test (EQ-5D) and Visual Analogue Scale (VAS), obtained from NeuroReg.

    Results: From September 2011 until April 2018, 1617 patients (67% female; 91% RRMS) were included in IMSE 2. At treatment start 38 patients were ≤20 years (yr), 308 aged 21-30 yr and 1271 aged >30 yr. Mean treatment duration was 34 months. 852 patients were currently treated with FGL at cut-off date and 1230 patients had been treated for at least 12 months. In total, 39% switched treatment from interferons or glatiramer acetate, 26% from natalizumab and 5% from dimethyl fumarate or teriflunomide. 803 patients have discontinued FGL at some point, mainly due to lack of effect (43%) or AEs (34%), most patients switched to rituximab after FGL discontinuation. Relapses were reduced from 281 to 87/1000 patient years (PY) when comparing before and during FGL treatment. In patients aged ≤20 yr, 21-30 yr and >30 yr relapses were reduced from 694 to 144/1000 PY, 455 to 129/1000 PY and 258 to 77/1000 PY, respectively. After 12 months significant improvements were seen in EQ-5D (0.7 to 0.8, n=752), MSSS (3.1 to 2.9, n=410), MSIS-29 Physical (21.1 to 20.0 n=812), MSIS-29 Psychological (29.2 to 24.9, n=812), SDMT (54.3 to 57.0, n=751) and VAS (70.9 to 72.8, n=692). When analysing age groups separately significant improvements were seen in MSSS, SDMT, and MSIS-29 Psychological in patients aged 21-30 yr and >30 yr. EQ-5D, VAS and MSIS-29 Physical significantly improved in patients aged >30 yr.

    Conclusions: FGL is a generally well-tolerated drug that reduces the clinical activity in MS patients. NeuroReg functions well as a drug surveillance platform, enabling monitoring of long-term effectiveness and AEs.

  • 18.
    Fält, A.
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Kågström, S.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Forsberg, L.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hillert, J.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, P.
    Department of Neurology, Lund University, Lund, Sweden.
    Dahle, C.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Svenningsson, A.
    Department of Clinical Science, Danderyd Hospital, Stockholm, Sweden.
    Lycke, J.
    Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Gothenburg, Sweden.
    Landtblom, A. -M
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Burman, J.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Martin, C.
    Department of Clinical Science, Danderyd Hospital, Stockholm, Sweden.
    Sundström, P.
    Department of Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Piehl, F.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Olsson, T.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    A swedish post-market surveillance study of the long-term effectiveness and safety of alemtuzumab (IMSE 3) for patients treated at least 24 months2019Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, nr Suppl. 2, s. 327-328Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Alemtuzumab (ALZ) is an approved disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS). Post-marketing surveillance is important to assess the long term safety and effectiveness in a real-world setting. ALZ has therefore been included into the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE) upon launch in Sweden (March 2014).

    Objective: To track effectiveness and long-term safety of ALZ in a real-world setting.

    Methods: Swedish MS patients are registered into the nationwide Swedish Neuro Registry (NeuroReg). IMSE 3 includes all patients starting ALZ treatment with annual clinical measures obtained from NeuroReg; Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - 5 Dimension Test (EQ-5D) and Visual Analogue Scale (VAS).

    Results: A total of 118 MS patients (59% female; 95% RRMS) were included in IMSE 3 between March 2014 and April 2019. 95 patients had started ALZ >24 months ago (63% female; 98% RRMS) at cut-off date (31st of Mars 2019), where only 3 patients had switched to another DMT. Mean age at treatment start for patients treated at least 24 months was 34 years and mean treatment duration was 42 months. Mean number of drugs prior ALZ initiation was 2.3. Most patients (41/95) switched to ALZ from natalizumab, while 14/95 patients were treatment naïve with ALZ. The number of relapses per 1,000 patient years decreased from 471 before ALZ initiation to 65 during ALZ treatment (n=83, missing data; n=12). In patients treated ⩾ 24 months significant improvements in mean were seen for EDSS (1.9 ± 1.4 to 1.6 ± 1.3, n=57), MSSS (3.3 ± 2.6 to 2.4 ± 2.1, n=48) and EQ-5D (0.7 ± 0.3 to 0.8 ± 0.3, n=53), while MSIS-29, SDMT and VAS scores remained stable. A total of 28 adverse events were reported to the Swedish Medical Products Agency, 12 events were classified as serious and 16 events as non-serious. Two patients died during ALZ treatment, of which one patient died in association with the first ALZ treatment cycle due to fulminant viral hepatitis.

    Conclusions: Patients treated with ALZ for at least 24 months improved or remained stable across all effectiveness measures. Only a very small percentage of patients switched to other DMTs. Continued follow-up is needed to address long term effectiveness and safety of ALZ.

  • 19.
    Fält, A.
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Kågström, S.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Forsberg, L.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hillert, J.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, P.
    Department of Neurology, Lund University, Lund, Sweden.
    Dahle, C.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Svenningsson, A.
    Department of Clinical Science, Danderyd, Hospital, Stockholm, Sweden.
    Lycke, J.
    Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Gothenburg, Sweden.
    Landtblom, A. -M
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Burman, J.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Martin, C.
    Department of Clinical Science, Danderyd, Hospital, Stockholm, Sweden.
    Sundström, P.
    Department of Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Piehl, F.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Olsson, T.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    A Swedish real word study of the long-term effectiveness and safety of fingolimod (IMSE 2) with focus on patients treated at least 48 months2019Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, nr Suppl. 2, s. 536-537Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Fingolimod (FGL) is an oral disease-modifying therapy (DMT) for patients with relapsing-remitting multiple sclerosis (RRMS) introduced in Sweden 2011. Already from launch FGL was included in the Swedish “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE) in order to enable long-term surveillance of effectiveness and safety aspects in a large population-based cohort.

    Objective: To track the effectiveness and long-term safety of FGL in a real-world setting.

    Methods: Swedish MS patients are registered into the nationwide Swedish Neuro Registry (NeuroReg). IMSE 2 includes patients starting FGL treatment and clinical and demographic data are collected from the NeuroReg. The Wilcoxon signed-rank test was used to assess changes in effectiveness measures.

    Results: From September 2011 until April 2019, 1652 MS patients (67% female; 90% RRMS) were included in IMSE 2. Mean age at treatment start was 39 years and mean treatment duration in the entire cohort was 39 months. 608 patients (64% female; 91% RRMS) had been treated with FGL for at least 48 months with a mean age at treatment start of 40 years and a mean treatment duration of 70 months. A majority (330/608) switched to FGL from interferons/glatiramer acetate, while 194/608 switched from natalizumab. 105/608 patients had discontinued FGL at some point, mainly due to lack of effect (31%) and adverse events (31%). Most patients (57/105) switched to rituximab after FGL discontinuation. The number of relapses per 1,000 patient years were reduced from 275 before FGL initiation to 40 during FGL treatment (27% missing data). In patients treated with FGL at least 48 months significant changes (mean) were seen in Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT) and Visual Analogue Scale (VAS). 80/184 patients had a 4-point or 10% increase in SDMT score between baseline and 48 months. In total 167 adverse events were reported to the Swedish Medical Products Agency of which 77 events were classified as serious.

    Conclusions: FGL displays a relatively high degree of drug persistence and clinical effectiveness is retained over time with significant improvements in MSSS, SDMT and VAS in patients treated at least 48 months. Furthermore, NeuroReg functions well as a drug surveillance platform, enabling monitoring of long-term effectiveness and safety.

  • 20.
    Granqvist, Mathias
    et al.
    Department of Clinical Neuroscience, Center for Molecular Medicine (CMM), Karolinska Institutet, Stockholm, Sweden.
    Burman, Joachim
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Lycke, Jan
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Nilsson, Petra
    Neurology Clinic, Skåne University Hospital, Lund, Sweden.
    Olsson, Tomas
    Department of Clinical Neuroscience, Center for Molecular Medicine (CMM), Karolinska Institutet, Stockholm, Sweden.
    Sundström, Peter
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Svenningsson, Anders
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Vrethem, Magnus
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Frisell, Thomas
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Piehl, Fredrik
    Department of Clinical Neuroscience, Center for Molecular Medicine (CMM), Karolinska Institutet, Stockholm, Sweden.
    Comparative effectiveness of dimethyl fumarate as the initial and secondary treatment for MS2019Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, artikel-id 1352458519866600Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Population-based real-world evidence studies of the effectiveness and tolerability of dimethyl fumarate in relation to common treatment alternatives are still limited.

    OBJECTIVE: To evaluate the clinical effectiveness and tolerability of dimethyl fumarate (DMF) as the initial and secondary treatment for relapsing-remitting multiple sclerosis (RRMS) patients compared with common treatment alternatives in Sweden.

    METHODS:  We conducted a nationwide retrospective observational cohort study of all RRMS patients identified through the Swedish MS registry initiating DMF (n = 641) or interferons/glatiramer acetate (IFN/GA; n = 555) as the initial therapy, or DMF (n = 703) or fingolimod (FGL; n = 194) after switch from IFN/GA between 1 January 2014 and 31 December 2016.

    RESULTS: The discontinuation rate was lower with DMF as the initial treatment than IFN/GA (adjusted hazard rate (HR): 0.46, 95% confidence interval (CI): 0.37-0.58, p < 0.001), but higher than FGL as the secondary treatment (HR: 1.51, CI: 1.08-2.09, p < 0.05). Annualized relapse rate (ARR) was lower with DMF compared to IFN/GA (0.04, CI: 0.03-0.06 vs 0.10, CI: 0.07-0.13; p < 0.05), but not FGL (0.03, CI: 0.02-0.05 vs 0.02, CI: 0.01-0.04; p = 0.41). Finally, time to first relapse (TTFR) was longer with DMF as the initial, but not secondary, therapy (p < 0.05 and p = 0.20, respectively).

    CONCLUSION: Our findings indicate that DMF performs better than IFN/GA as the initial treatment for RRMS. Compared to FGL, DMF displayed a lower tolerability, but largely similar effectiveness outcomes.

  • 21.
    Gunnarsson, Martin
    et al.
    Örebro universitet, Institutionen för läkarutbildning.
    Udumyan, Ruzan
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Bahmanyar, S.
    Clinical Epidemiology Unit and Centre for Pharmacoepidemiology, Department of Medicine, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden; Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran .
    Nilsagård, Ylva
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Montgomery, Scott
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Research Department of Epidemiology and Public Health, University College London, London, United Kingdom .
    Characteristics in childhood and adolescence associated with future multiple sclerosis risk in men: cohort study2015Ingår i: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 22, nr 7, s. 1131-1137Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and purpose: Associations with multiple sclerosis (MS) of living conditions in childhood and characteristics in adolescence including physical fitness, cognitive function and psychological stress resilience were investigated.

    Methods: A cohort of male Swedish residents born 1952-1956 who were included in the Swedish Military Conscription Register was used to create a nested case-control study comprising 628 MS cases and 6187 controls matched on birth year, county of residence and vital status at time of diagnosis. Conscription examination records were linked with other national register data. Conditional logistic regression was used to evaluate associations with MS subsequent to the conscription examination.

    Results and conclusions: Men with MS were less likely to be from more crowded households in childhood (>two persons per room) with an adjusted odds ratio of 0.67 (95% confidence interval 0.51-0.86, P=0.023). They had lower physical working capacity in adolescence with adjusted odds ratio of 0.94 (95% confidence interval 0.89-0.99, P=0.026). Cognitive function and stress resilience scores displayed no significant differences between cases and controls. Parental occupation in childhood and body mass index in adolescence were not associated with future MS risk. The inverse association of MS risk with higher levels of household crowding may reflect environmental factors such as the pattern of exposure to microorganisms. Lower physical fitness in men at MS risk may indicate a protective effect of exercise or could be due to prodromal disease activity, although there was no association with cognitive function. Poor psychological stress resilience (and thus risk of chronic stress arousal) was not associated with MS.

  • 22.
    Krauss, Wolfgang
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för läkarutbildning.
    Andersson, Torbjorn
    Örebro universitet, Institutionen för läkarutbildning.
    Thunberg, Per
    Department of Medical Physics, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Accuracy and reproducibility of a quantitative magnetic resonance imaging method for concurrent measurements of tissue relaxation times and proton density2015Ingår i: Magnetic Resonance Imaging, ISSN 0730-725X, E-ISSN 1873-5894, Vol. 33, nr 5, s. 584-591Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To evaluate the accuracy and reproducibility of a quantitative magnetic resonance (qMR) imaging method (QRAPMASTER) for simultaneous measurements of T1 and T2 relaxation times, and proton density (PD).

    Materials and Methods: Measurements of T1, T2, and PD with qMR were performed using phantoms with different relaxation times and concentrations of heavy water. Healthy volunteers were examined with different head coils. Regional measurements were performed in normal-appearing white and gray matter from the healthy control subjects, and in multiple sclerosis (MS) patients.

    Results: In phantom measurements, QRAPMASTER slightly underestimated T1, and T2 variations between repeated measurements were modest. PD was generally overestimated. The overall relative difference was 1.2 5.3% (T1), 6.6 1.9% (12), and 0.7 5.1% (PD). In healthy volunteers, there were no statistically significant differences of T1, T2 or PD using different head coils. Values of T1, T2, and PD obtained in healthy controls and MS patients were within reference ranges. However, significant differences were found in normal-appearing gray and white matter.

    Conclusion: QRAPMASTER can be considered a sufficiently accurate and reproducible method for use in clinical practice. Neuropathology in normal-appearing brain tissue may be revealed using this MR method, with putative implications for quantification of tissue damage in neurological diseases. (C) 2015 Elsevier Inc. All rights reserved.

  • 23.
    Krauss, Wolfgang
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Radiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology and Neurophysiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Nilsson, Margareta
    Centre for Medical Imaging and Physiology, Skåne University Hospital, Lund, Sweden.
    Thunberg, Per
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Medical Physics, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Conventional and synthetic MRI in multiple sclerosis: a comparative study2018Ingår i: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 28, nr 4, s. 1692-1700Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To compare the assessment of patients with multiple sclerosis (MS) using synthetic and conventional MRI.

    MATERIALS AND METHODS: Synthetic and conventional axial images were prospectively acquired for 52 patients with diagnosed MS. Quantitative MRI (qMRI) was used for measuring proton density and relaxation times (T1, T2) and then, based on these parameters, synthetic T1W, T2W and FLAIR images were calculated. Image stacks were reviewed blindly, independently and in random order by two radiologists. The number and location for all lesions were documented and categorised. A combined report of lesion load and presence of contrast-enhancing lesions was compiled for each patient. Agreement was evaluated using kappa statistic.

    RESULTS: There was no significant difference in lesion detection using synthetic and conventional MRI in any anatomical region or for any of the three image types. Inter- and intra-observer agreements were mainly higher (p < 0.05) using conventional images but there was no significant difference in any specific region or for any image type. There was no significant difference in the outcome of the combined reports.

    CONCLUSION: Synthetic MR images show potential to be used in the assessment of MS dissemination in space (DIS) despite a slightly lower inter- and intra-observer agreement compared to conventional MRI.

    KEY POINTS:

    • Synthetic MR images may potentially be useful in the assessment of MS.

    • Examination times may be shortened.

    • Inter- and intra-observer agreement is generally higher using conventional MRI.

  • 24.
    Kågström, S.
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Fält, A.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Demirbuker, S. Safer
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Berglund, A.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hillert, J.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, P.
    Department of Neurology, Lund University, Lund, Sweden.
    Dahle, C.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Svenningsson, A.
    Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
    Lycke, J.
    Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Göteborg, Sweden.
    Landtblom, A. -M
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Burman, J.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Martin, C.
    Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
    Sundström, P.
    Department of Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Piehl, F.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Olsson, T.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Real-world longitudinal data of peginterferon beta-1a from a Swedish national post-marketing surveillance study (IMSE 6) - efficacy and safety profile2018Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, nr Suppl. 2, s. 927-928Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Subcutaneous peginterferon beta-1a (PegIFN) was approved for relapsing-remitting multiple sclerosis (RRMS) in Europe 2014. Phase II and III studies have shown that PegIFN reduces relapse rate and reduces the tendency to deteriorate disabilities. However, the long-term safety is important, therefore PegINF is included in the Swedish “Immunomodulation and Multiple Sclerosis Epidemiology Study 6” (IMSE 6). Which characterizes the real-world profile of PegIFN, including efficacy, safety, tolerability and patient outcome parameters.

    Objectives: To follow-up the long-term safety and effectiveness of PegIFN in a real-world setting.

    Methods: Approximately 60 collaborating neurology clinics continuously recruited PegIFN patients and documented clinical and demographic data in the nationwide Swedish Neuro Registry (NeuroReg). Data were obtained from NeuroReg between June 2015 and April 2018 for the IMSE 6 study.

    Results: A total of 324 patients (78% female; 88% RRMS; mean age at treatments start 43 years) were followed up to 34 months (mean 15 months) with 26% treatment naïve and 49% switched from other injectables. Mean duration from initial symptom(s) to treatment start was 114 months, and 69 months from MS diagnosis to treatment start. In total, 169 patients discontinued for vari-ous reasons (60% adverse events, 24% lack of effect) and switched mainly to rituximab (63 patients, 37%). The discontinuation rate at 12 months was 42.6%. Relapses before treatment were reduced from 207 to 130/1000 patient years during treatment. With 55% having no relapse and 9% having 1 relapse during treatment period (35% missing data). After 12 months, all clinical effectiveness measures (Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - 5-Dimension test (EQ-5D), Visual Analogue Score (VAS), and the mean Symbol Digit Modalities Test (SDMT)) remained stable. A total number of 9 adverse events (6 serious: 1 gastrointestinal disorder, 2 general disorder and administrations site, 2 skin, 1 reproductive) were reported to Swedish Medical Product Agency (MPA).

    Conclusions: NeuroReg proves to function well as a post-marketing drug surveillance platform, providing data regarding drug effectiveness and AEs. This real-world study presentation from IMSE 6 shows a stable efficacy and safety profile in long-term clinical use.

  • 25.
    Kågström, S.
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Fält, A.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Demirbüker, S. Safer
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Berglund, A.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hillert, J.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, P.
    Department of Neurology, Lund University, Lund, Sweden.
    Dahle, C.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Svenningsson, A.
    Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
    Lycke, J.
    Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Göteborg, Sweden.
    Landtblom, A. -M
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Burman, J.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Martin, C.
    Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
    Sundström, P.
    Department of Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Piehl, F.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Olsson, T.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    A Swedish nationwide pharmaco-epidemiological and genetic study of the long-term safety and effectiveness of natalizumab (IMSE 1)2018Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, nr Suppl. 2, s. 699-700Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Natalizumab (NTZ) is a highly effective disease modulatory treatment for relapsing-remitting multiple sclerosis (RRMS). Post-marketing surveillance is important for determination of long-term safety and effectiveness in a real-world setting. To this end the “Immunomodulation and Multiple Sclerosis Epidemiology Study 1” (IMSE 1) was initiated upon NTZ launch in Sweden (Aug 2006).

    Objective: To follow-up the long-term safety and effectiveness of NTZ in a real-world setting.

    Methods: In Sweden MS patients are registered in the nationwide Swedish Neuro Registry (NeuroReg). IMSE 1 includes patients starting NTZ treatment and data is collected from NeuroReg. Adverse events (AEs), JC-virus status (JCV) and clinical effectiveness measures are registered prospectively.

    Results: 3052 patients (72% female; 82% RRMS; mean age at treatment start 36 years; mean treatment duration 45.9 months) have been included in IMSE 1 from August 2006 until April 2018. A total of 1234 RRMS patients where included year ≥2011 (JCV test introduction) and had information on JCV (482 anti-JCV anti-bodies (JCV+), 752 JCV negative (JCV-)). 691 of these patients were currently treated with NZT at cutoff date, 88 (13%) of which were JCV+ with a mean JCV index at 1.1±1.1. A total of 612/1234 (49%) discontinued NTZ treatment at some time point of which 266/403 (66%) JCV+ discontinued due to JCV+. JCV- patients mainly discontinued due to pregnancy/planning pregnancy (78/209, 37%) and other reasons (57/209, 27%). The one and two-year drug survival rate was 79% and 45% for JCV+ and 90% and 82% for JCV-. The overall drug survival rate was 16% for JCV+ and 72% for JCV-. In patients with continuous NTZ treatment for ≥2 years (n=738), long lasting stabilization of disease activity was observed. From year 2006 until cutoff, 96 Serious AEs had been reported to the Swedish MPA and included 8 cases (1 fatal) of progressive multifocal leukoencephalopathy (PML), reported between 2008 and 2012. A total of 14 patients have died during or within 6 months after NTZ discontinuation, as reported in NeuroReg. None were reported to be associated to NTZ.

    Conclusions: NeuroReg functions well as a post-marketing drug surveillance platform, providing long-term data on drug effects and AEs. NTZ is generally well tolerated with sustained effective-ness. The introduction of JCV testing has led to fewer treated JCV+ patients, which likely explains a reduced incidence of PML.

  • 26.
    Kågström, S.
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Fält, A.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Forsberg, L.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Berglund, A.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hillert, J.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, P.
    Department of Neurology, Lund University, Lund, Sweden.
    Dahle, C.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Svenningsson, A.
    Department of Clinical Science, Danderyd Hospital, Stockholm, Sweden.
    Lycke, J.
    Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Göteborg, Sweden.
    Landtblom, A. -M
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Burman, J.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Sundström, P.
    Department of Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Martin, C.
    Department of Clinical Science, Danderyd Hospital, Stockholm, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Piehl, F.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Olsson, T.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Improved clinical outcomes in patients treated with natalizumab for at least 8 years - real-world data from a Swedish national post-marketing surveillance study (IMSE 1)2019Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, nr Suppl. 2, s. 763-764Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Natalizumab (NTZ) is a highly effective disease modulatory treatment for relapsing-remitting multiple sclerosis (RRMS). Post-marketing surveillance is important for evaluation of long-term safety and effectiveness in a real-world setting. To this end the “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE 1) was initiated upon NTZ launch in Sweden (Aug 2006).

    Objective: To follow-up the long-term effectiveness and safety of NTZ in a real-world setting.

    Methods: In Sweden MS patients are registered in the nationwide Swedish Neuro Registry (NeuroReg). IMSE 1 includes patients starting NTZ treatment and data is collected from NeuroReg. Adverse events (AEs), JC-virus status (JCV) and clinical effec-tiveness measures are registered prospectively.

    Results: A total of 3141 patients were included in the IMSE 1 study from August 2006 until April 2019 (72% female; men age 35 years; 79% RRMS; mean treatment duration 50 months) and 288 had been treated for at least 96 months. 71% of these 288 patients (71% female; men age 37 years; 82% RRMS; mean treatment duration 118 months) were treated with interferons and glatiramer acetate prior NTZ. At some point of time, 31% (90/288) discontin-ued NTZ treatment of which 41% discontinued due to JCV posi-tive (JCV+). In total, 30% (86/288) of these patients were JCV+with a mean JCV index of 1.2±1.0 (6% missing data). Relapses before treatment were reduced from 388/1000 patient years to 54 during treatment, 62% were relapse-free and 17% had 1 relapse during the entire treatment period (12% missing data). All clinical effectiveness measures (Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Multiple Sclerosis Impact Scale (MSIS-29) and Symbol Digit Modalities Test (SDMT)) showed statistically significant improvement between baseline and 96 months. Over the entire observation time, 104 Serious AEs had been reported to the Swedish MPA and included 9 cases (2 fatal) of progressive multifocal leukoencephalopathy (PML) of which 8 between 2008 and 2012, and 1in 2018. 16 patients died during or within 6 months of last NTZ infusion. None were judged to be directly associated with NTZ.

    Conclusions: NTZ is generally well tolerated with sustained effectiveness regarding cognitive, physical and psychological measures, as well as relapse-control. Introduction of JCV testing has led to fewer treated JCV+ patients, which likely explains a drastic drop in the incidence of PML.

  • 27.
    Luna, Gustavo
    et al.
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Alping, Peter
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Burman, Joachim
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Fink, Katharina
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Fogdell-Hahn, Anna
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Hillert, Jan
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Langer-Gould, Annette
    Clinical and Translational Neuroscience, Southern California Permanente Medical Group, Kaiser Permanente, Pasadena.
    Lycke, Jan
    Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Gothenburg, Sweden.
    Nilsson, Petra
    Department of Clinical Sciences, Division of Neurology, Lund University, Lund, Sweden.
    Salzer, Jonatan
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Svenningsson, Anders
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Vrethem, Magnus
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Olsson, Tomas
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Piehl, Fredrik
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Academic Specialist Center, Stockholm Health Services, Stockholm, Sweden.
    Frisell, Thomas
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Infection Risks Among Patients With Multiple Sclerosis Treated With Fingolimod, Natalizumab, Rituximab, and Injectable Therapies2019Ingår i: JAMA Neurology, ISSN 2168-6149, E-ISSN 2168-6157Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Importance: Although highly effective disease-modifying therapies for multiple sclerosis (MS) have been associated with an increased risk of infections vs injectable therapies interferon beta and glatiramer acetate (GA), the magnitude of potential risk increase is not well established in real-world populations. Even less is known about infection risk associated with rituximab, which is extensively used off-label to treat MS in Sweden.

    Objective: To examine the risk of serious infections associated with disease-modifying treatments for MS.

    Design, Setting, and Participants: This nationwide register-based cohort study was conducted in Sweden from January 1, 2011, to December 31, 2017. National registers with prospective data collection from the public health care system were used. All Swedish patients with relapsing-remitting MS whose data were recorded in the Swedish MS register as initiating treatment with rituximab, natalizumab, fingolimod, or interferon beta and GA and an age-matched and sex-matched general population comparator cohort were included.

    Exposures: Treatment with rituximab, natalizumab, fingolimod, and interferon beta and GA.

    Main Outcomes and Measures: Serious infections were defined as all infections resulting in hospitalization. Additional outcomes included outpatient treatment with antibiotic or herpes antiviral medications. Adjusted hazard ratios (HRs) were estimated in Cox regressions.

    Results: A total of 6421 patients (3260 taking rituximab, 1588 taking natalizumab, 1535 taking fingolimod, and 2217 taking interferon beta/GA) were included, plus a comparator cohort of 42 645 individuals. Among 6421 patients with 8600 treatment episodes, the mean (SD) age at treatment start ranged from 35.0 (10.1) years to 40.4 (10.6) years; 6186 patients were female. The crude rate of infections was higher in patients with MS taking interferon beta and GA than the general population (incidence rate, 8.9 [95% CI, 6.4-12.1] vs 5.2 [95% CI, 4.8-5.5] per 1000 person-years), and higher still in patients taking fingolimod (incidence rate, 14.3 [95% CI, 10.8-18.5] per 1000 person-years), natalizumab (incidence rate, 11.4 [95% CI, 8.3-15.3] per 1000 person-years), and rituximab (incidence rate, 19.7 [95% CI, 16.4-23.5] per 1000 person-years). After confounder adjustment, the rate remained significantly higher for rituximab (HR, 1.70 [95% CI, 1.11-2.61]) but not fingolimod (HR, 1.30 [95% CI, 0.84-2.03]) or natalizumab (HR, 1.12 [95% CI, 0.71-1.77]) compared with interferon beta and GA. In contrast, use of herpes antiviral drugs during rituximab treatment was similar to that of interferon beta and GA and lower than that of natalizumab (HR, 1.82 [1.34-2.46]) and fingolimod (HR, 1.71 [95% CI, 1.27-2.32]).

    Conclusions and Relevance: Patients with MS are at a generally increased risk of infections, and this differs by treatment. The rate of infections was lowest with interferon beta and GA; among newer treatments, off-label use of rituximab was associated with the highest rate of serious infections. The different risk profiles should inform the risk-benefit assessments of these treatments.

  • 28.
    Nilsagård, Ylva
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Ctr Hlth Care Sci, Örebro Univ Hosp, Örebro, Sweden.
    Westerdahl, Elisabeth
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Wittrin, A.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för läkarutbildning.
    Correlation between maximal walking distance and self-rated limitations in walking2014Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, nr 7, s. 992-992Artikel i tidskrift (Övrigt vetenskapligt)
  • 29.
    Nilsagård, Ylva
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Westerdahl, Elisabeth
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Wittrin, Anna
    Department of Neurology, Örebro University Hospital, Örebro, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för läkarutbildning. Department of Neurology, Örebro University Hospital, Örebro, Sweden.
    Walking Distance as a Predictor of Falls in People With Multiple Sclerosis2016Ingår i: Physiotherapy Research International, ISSN 1358-2267, E-ISSN 1471-2865, Vol. 21, nr 2, s. 102-108Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and purpose: People with multiple sclerosis (PwMS) experience falls, usually when walking and transferring. The aim was to investigate if walking distance and patient overestimate of walking distance are predictors of falls in PwMS.

    Methods: A prospective study was conducted, with a single test occasion followed by prospective registration of falls for 3 months. All PwMS in Region Örebro County with a previously registered Expanded Disability Status Scale score between 3.0 and 7.0 in the Swedish MS Registry were invited to participate (n = 149). Altogether, data from 49 PwMS being relapse free for at least 3 months and with a confirmed Expanded Disability Status Scale between 1.5 and 7.0 upon study entry were analysed.

    Results: Twenty-two PwMS (45%) fell during the study period, providing information of 66 falls. Walking distance or overestimate of one's walking distance, as compared with test results, did not predict falls in this MS sample.

    Discussion: Walking and standing activities are associated with numerous falls in PwMS. Our data do not clearly support routine measurements of walking distance in assessing individual fall risk.

  • 30.
    Novakova, L.
    et al.
    Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg, Sweden.
    Zetterberg, H.
    Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg, Sweden.
    Axelsson, M.
    Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg, Sweden.
    Sundström, P.
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Khademi, M.
    Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Malmeström, C.
    Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg, Sweden.
    Svenningsson, A.
    Department of Clinical Sciences Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
    Olsson, T.
    Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Piehl, F.
    Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Blennow, K.
    Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg, Sweden.
    Lycke, J.
    Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg, Sweden.
    Neurofilament light in serum for monitoring multiple sclerosis: A new quantitative tool for measuring disease activity and therapeutic response2017Ingår i: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 24, nr Suppl. 1, s. 577-577, artikel-id PR2087Artikel i tidskrift (Övrigt vetenskapligt)
  • 31.
    Novakova, Lenka
    et al.
    Department of Clinical Neuroscience Institute of Neuroscience and Physiology,t Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Zetterberg, Henrik
    Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
    Sundström, Peter
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Axelsson, Markus
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Khademi, Mohsen
    Department of Clinical Neuroscience, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Malmeström, Clas
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Svenningsson, Anders
    Neuroimmunology Unit, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Olsson, Tomas
    Department of Clinical Neuroscience, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Piehl, Fredrik
    Department of Clinical Neuroscience, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Blennow, Kaj
    Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
    Lycke, Jan
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Monitoring disease activity in multiple sclerosis using serum neurofilament light protein2017Ingår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 89, nr 22, s. 2230-2237, artikel-id 10.1212/WNL.0000000000004683Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To examine the effects of disease activity, disability, and disease-modifying therapies (DMTs) on serum neurofilament light (NFL) and the correlation between NFL concentrations in serum and CSF in multiple sclerosis (MS).

    METHODS: NFL concentrations were measured in paired serum and CSF samples (n = 521) from 373 participants: 286 had MS, 45 had other neurologic conditions, and 42 were healthy controls (HCs). In 138 patients with MS, the serum and CSF samples were obtained before and after DMT treatment with a median interval of 12 months. The CSF NFL concentration was measured with the UmanDiagnostics NF-light enzyme-linked immunosorbent assay. The serum NFL concentration was measured with an in-house ultrasensitive single-molecule array assay.

    RESULTS: In MS, the correlation between serum and CSF NFL was r = 0.62 (p < 0.001). Serum concentrations were significantly higher in patients with relapsing-remitting MS (16.9 ng/L) and in patients with progressive MS (23 ng/L) than in HCs (10.5 ng/L, p < 0.001 and p < 0.001, respectively). Treatment with DMT reduced median serum NFL levels from 18.6 (interquartile range [IQR] 12.6-32.7) ng/L to 15.7 (IQR 9.6-22.7) ng/L (p < 0.001). Patients with relapse or with radiologic activity had significantly higher serum NFL levels than those in remission (p < 0.001) or those without new lesions on MRI (p < 0.001).

    CONCLUSIONS: Serum and CSF NFL levels were highly correlated, indicating that blood sampling can replace CSF taps for this particular marker. Disease activity and DMT had similar effects on serum and CSF NFL concentrations. Repeated NFL determinations in peripheral blood for detecting axonal damage may represent new possibilities in MS monitoring.

  • 32.
    Vågberg, M.
    et al.
    Department of Pharmacology and Clinical Neuroscience, Section of Neuroscience, Umeå University, Umeå, Sweden.
    Axelsson, M.
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Birgander, R.
    Department of Radiation Sciences, Umeå University, Umeå, Sweden.
    Burman, J.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Cananau, C.
    Department of Clinical Science, Intervention and Technology, Department of Radiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Forslin, Y.
    Department of Clinical Science, Intervention and Technology, Department of Radiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Granberg, T.
    Department of Clinical Science, Intervention and Technology, Department of Radiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    von Heijne, A.
    Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
    Jönsson, L.
    Department of Neuroradiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Karrenbauer, V. D.
    Department of Clinical Neuroscience, Department of Neurology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Larsson, E.-M.
    Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden.
    Lindqvist, T.
    Department of Radiation Sciences, Umeå University, Umeå, Sweden.
    Lycke, J.
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Lönn, L.
    Department of Clinical Science, Intervention and Technology, Department of Radiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Mentesidou, E.
    Department of Clinical Neuroscience, Department of Neurology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Müller, S.
    Department of Clinical Science, Intervention and Technology, Department of Radiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Nilsson, P.
    Department of Clinical Sciences Lund, Neurology, Faculty of Medicine, Lund University, Lund, Sweden.
    Piehl, F.
    Department of Clinical Neuroscience, Department of Neurology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Svenningsson, A.
    Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
    Vrethem, M.
    Department of Neurology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Wikström, J.
    Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden.
    Guidelines for the use of magnetic resonance imaging in diagnosing and monitoring the treatment of multiple sclerosis: recommendations of the Swedish Multiple Sclerosis Association and the Swedish Neuroradiological Society2017Ingår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 135, nr 1, s. 17-24Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Multiple sclerosis (MS) is associated with inflammatory lesions in the brain and spinal cord. The detection of such inflammatory lesions using magnetic resonance imaging (MRI) is important in the consideration of the diagnosis and differential diagnoses of MS, as well as in the monitoring of disease activity and predicting treatment efficacy. Although there is strong evidence supporting the use of MRI for both the diagnosis and monitoring of disease activity, there is a lack of evidence regarding which MRI protocols to use, the frequency of examinations, and in what clinical situations to consider MRI examination. A national workshop to discuss these issues was held in Stockholm, Sweden, in August 2015, which resulted in a Swedish consensus statement regarding the use of MRI in the care of individuals with MS. The aim of this consensus statement is to provide practical advice for the use of MRI in this setting. The recommendations are based on a review of relevant literature and the clinical experience of workshop attendees. It is our hope that these recommendations will benefit individuals with MS and guide healthcare professionals responsible for their care.

  • 33.
    Westerdahl, Elisabeth
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län. Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Wittrin, Anna
    Faculty of Medicine and Health, Department of Neurology and Neurophysiology, Örebro University, Örebro, Sweden.
    Kånåhols, Margareta
    Faculty of Medicine and Health, Department of Neurology and Neurophysiology, Örebro University, Örebro, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för läkarutbildning. Region Örebro län. Department of Neurology and Neurophysiology, Örebro University Hospital, Örebro, Sweden.
    Nilsagård, Ylva
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län.
    Deep breathing exercises with positive expiratory pressure in patients with multiple sclerosis: a randomized controlled trial2016Ingår i: Clinical Respiratory Journal, ISSN 1752-6981, E-ISSN 1752-699X, Vol. 10, nr 6, s. 698-706Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Breathing exercises with positive expiratory pressure are often recommended to patients with advanced neurological deficits, but the potential benefit in multiple sclerosis (MS) patients with mild and moderate symptoms has not yet been investigated in randomized controlled trials.

    Objectives: To study the effects of 2 months of home-based breathing exercises for patients with mild to moderate MS on respiratory muscle strength, lung function, and subjective breathing and health status outcomes.

    Methods: Forty-eight patients with MS according to the revised McDonald criteria were enrolled in a randomized controlled trial. Patients performing breathing exercises (n = 23) were compared with a control group (n = 25) performing no breathing exercises. The breathing exercises were performed with a positive expiratory pressure device (10-15 cmH2 O) and consisted of 30 slow deep breaths performed twice a day for 2 months. Respiratory muscle strength (maximal inspiratory and expiratory pressure at the mouth), spirometry, oxygenation, thoracic excursion, subjective perceptions of breathing and self-reported health status were evaluated before and after the intervention period.

    Results: Following the intervention, there was a significant difference between the breathing group and the control group regarding the relative change in lung function, favoring the breathing group (vital capacity: P < 0.043; forced vital capacity: P < 0.025). There were no other significant differences between the groups.

    Conclusion: Breathing exercises may be beneficial in patients with mild to moderate stages of MS. However, the clinical significance needs to be clarified, and it remains to be seen whether a sustainable effect in delaying the development of respiratory dysfunction in MS can be obtained.

  • 34.
    Wittrin, A.
    et al.
    Örebro Univ Hosp, Örebro, Sweden.
    Nilsagård, Ylva
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Westerdahl, Elisabeth
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för läkarutbildning. Örebro Univ Hosp, Örebro, Sweden.
    Self-assessment of walking ability in patients with multiple sclerosis and its impact on the expanded disability status scale (EDSS) score2013Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, nr 11, s. 118-118Artikel i tidskrift (Övrigt vetenskapligt)
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