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  • 1.
    Salzer, Jonatan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Granåsen, Gabriel
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Vågberg, Mattias
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences. Department of Clinical Sciences, Danderyd Hospital AB, Karolinska Institutet Danderyd Hospital, Stockholm,Sweden.
    Prevention of post-dural puncture headache: a randomized controlled trial2020In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331Article in journal (Refereed)
    Abstract [en]

    Background and purpose: We investigated 952 subjects undergoing diagnostic lumbar puncture (LP) to study the effects of needle size, needle design and stylet reinsertion on the risk of post‐dural puncture headache (PDPH).

    Methods: This randomized double‐blind study was performed at Umeå University Hospital in Sweden during 2013–2018. Subjects were randomly assigned one of three needles [22 gauge (G) atraumatic, 25G atraumatic and 25G cutting] and stylet reinsertion before needle withdrawal or not. The main outcome measure was PDPH assessed by standardized telephone interview(s) 5 days after the LP, repeated until headache cessation. We used logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CI) for PDPH.

    Results: The mean (SD) age was 51.1 (16.7) years and 53.6% were females. The smaller bore (25G) atraumatic needle incurred a lower risk of headache compared with the larger bore (22G) atraumatic needle [22.0% (69/314) vs. 30.2% (98/324); OR, 0.65; 95% CI, 0.45–0.93] and compared with the cutting needle [32.8% (103/314); OR, 0.58; 95% CI, 0.40–0.82]. Reinserting the stylet before needle withdrawal did not reduce the risk of headache.

    Conclusions: These data suggest that a 25G atraumatic needle is superior to a larger atraumatic needle, and to a same‐sized cutting needle, in preventing PDPH after diagnostic LP. In contrast to one earlier report, this study did not find that stylet reinsertion was effective in preventing PDPH. This study provides class I evidence that a small atraumatic needle decreases the risk of PDPH and that stylet reinsertion does not influence PDPH risk.

  • 2.
    Salzer, Jonatan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Rajda, C.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Vågberg, Mattias
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Vecsei, L.
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Are we minimizing the patients' risk for headache?: a lumbar puncture practice questionnaire study among European neurologists2015In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, p. 733-734Article in journal (Other academic)
  • 3.
    Salzer, Jonatan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Rajda, Cecilia
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Vågberg, Mattias
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Vecsei, Laszlo
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    How to minimize the risk for headache?: a lumbar puncture practice questionnaire study2016In: IDEGGYOGYASZATI SZEMLE-CLINICAL NEUROSCIENCE, ISSN 0019-1442, Vol. 69, no 11-12, p. 397-402Article in journal (Refereed)
    Abstract [en]

    Background - To lower the risk for post lumbar puncture (LP) headache the American Academy of Neurology (AAN) recommended using small bore atraumatic needles together with stylet reinsertion in a report from 2005. It is unclear whether these recommendations are followed or not. Objectives To investigate the diagnostic LP preferences with respect to the AAN guidelines among neurologists by use of a short online questionnaire, and to review previously published literature on the subject. Results - A total of 284 respondents who performed diagnostic LPs completed the questionnaire. Almost half (41%) answered that they always use atraumatic needles. The most common reason (73%) for not using atraumatic needles was that these were not available. Less than half of the respondents who performed LPs had knowledge about the MN guidelines for diagnostic LPs, and 48-76% agreed with the different recommendations therein. Five previously (1998-2015) published studies investigating LP practice among neurologists were identified. The reported frequency of atraumatic needle use (always/routinely) varied between 2 and 16%. Discussion - Atraumatic needle use was more common in this study compared with previous publications. There is still skepticism regarding some of the MN recommendations, and needle availability appears to be the most important factor preventing atraumatic needle use. To increase the use of atraumatic needles we may perform additional studies investigating their potential benefits, and arrange training sessions for neurologists to increase their awareness and level of comfort with the atraumatic LP technique.

  • 4.
    Salzer, Jonatan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Vågberg, Mattias
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Lumbar puncture preferences among Swedish neurologists.2015In: Neurological Research, ISSN 0161-6412, E-ISSN 1743-1328, Vol. 37, no 1, p. 92-4Article in journal (Refereed)
    Abstract [en]

    Lumbar puncture (LP) with cerebrospinal fluid analysis is a common diagnostic tool in neurology, and may be complicated by post-LP headache (PLPHA). The American Academy of Neurology (AAN) has published guidelines for performing diagnostic LPs with the aim to reduce PLPHA risk, but our clinical hands-on experience suggests that these are not followed. We performed a questionnaire study among Swedish neurologists to investigate the acceptance and implementation of the AAN guidelines. Only one-eighth (22/174) of the respondents performed their LPs according to the AAN guidelines. The poor adherence to the AAN guidelines among Swedish neurologists may be due to perceived low credibility, as the current guidelines cite only one study to support the recommendation to use atraumatic needles, and only one study to support the recommendation to replace the stylet before needle withdrawal. An international survey has been posted ( https://www.surveymonkey.com/s/lumbarpuncturesurvey ) to investigate whether the results of this Swedish questionnaire are representative of neurologists worldwide.

  • 5.
    Salzer, Jonatan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Svenningsson, Rasmus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Department of Clinical Neuroscience, Danderyd Hospital, Karolinska Institutet, Stockholm.
    Alping, Peter
    Novakova, Lenka
    Björck, Anna
    Fink, Katharina
    Islam-Jakobsson, Protik
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Malmeström, Clas
    Axelsson, Markus
    Vågberg, Mattias
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Lycke, Jan
    Piehl, Fredrik
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm.
    Rituximab in multiple sclerosis: a retrospective observational study on safety and efficacy2016In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 87, no 20, p. 2074-2081Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the safety and efficacy of rituximab in multiple sclerosis (MS). Methods: In this retrospective uncontrolled observational multicenter study, off-label rituximab-treated patients with MS were identified through the Swedish MS register. Outcome data were collected from the MS register and medical charts. Adverse events (AEs) grades 2-5 according to the Common Terminology Criteria for Adverse Events were recorded. Results: A total of 822 rituximab-treated patients with MS were identified: 557 relapsing-remitting MS (RRMS), 198 secondary progressive MS (SPMS), and 67 primary progressive MS (PPMS). At baseline, 26.2% had contrast-enhancing lesions (CELs). Patients were treated with 500 or 1,000 mg rituximab IV every 6-12 months, during a mean 21.8 (SD 14.3) months. During treatment, the annualized relapse rates were 0.044 (RRMS), 0.038 (SPMS), and 0.015 (PPMS), and 4.6% of patients displayed CELs. Median Expanded Disability Status Scale remained unchanged in RRMS (p = 0.42) and increased by 0.5 and 1.0 in SPMS and PPMS, respectively (p = 0.10 and 0.25). Infusion-related AEs occurred during 7.8% of infusions and most were mild. A total of 89 AEs grades >= 2 (of which 76 infections) were recorded in 72 patients. No case of progressive multifocal leukoencephalopathy was detected. Conclusions: This is the largest cohort of patients with MS treated with rituximab reported so far. The safety, clinical, and MRI findings in this heterogeneous real-world cohort treated with different doses of rituximab were similar to those reported in previous randomized controlled trials on B-cell depletion therapy in MS. Classification of evidence: This study provides Class IV evidence that for patients with MS, rituximab is safe and effective.

  • 6.
    Sandberg, L.
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Bistrom, M.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Salzer, Jonatan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Vagberg, Mattias
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Sundstrom, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Vitamin D and axonal injury in multiple sclerosis2016In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 22, no 8, p. 1027-1031Article in journal (Refereed)
    Abstract [en]

    Background: Previous studies in patients with multiple sclerosis (MS) have shown an association between high serum 25-hydroxyvitamin D (25[OH]D) levels and decreased inflammatory activity. Objective: The purpose of this study was to examine the association between 25(OH)D levels and axonal injury in MS. Cerebrospinal fluid neurofilament light (CSF-NFL) was used as a marker for axonal injury. Methods: Patients were identified through clinical practice at the Department of Neurology in Umea University Hospital, Sweden. Blood draw, magnetic resonance imaging, scoring of disability and lumbar puncture were performed at inclusion in 153 patients, and also at median 12 months follow-up in 87 patients. For analyses of serum 25(OH)D levels and CSF-NFL, enzyme-linked immunosorbent assays were used. Results: There was an inverse association between serum 25(OH)D and CSF-NFL levels in categorical (dichotomized at 75 or 100 nmol/l) analyses. A dose-response effect for 25(OH)D levels on CSF-NFL levels (p for trend=0.034) was also present. Serum 25(OH)D levels above 100 nmol/l were associated with lower CSF-NFL levels independently of ongoing MS treatment. Conclusion: High 25(OH)D levels are associated with decreased axonal injury in MS.

  • 7.
    Svenningsson, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Bergman, Joakim
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Dring, Ann
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Vågberg, Mattias
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Lindqvist, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Gilthorpe, Jonathan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Bergenheim, Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Rapid depletion of B lymphocytes by ultra-low-dose rituximab delivered intrathecally2015In: Neurology: Neuroimmunology and neuroinflammation, ISSN 0948-6259, E-ISSN 2332-7812, Vol. 2, no 2, article id e79Article in journal (Refereed)
    Abstract [en]

    Objective: We are conducting an open-label phase 1b study on the efficacy of intrathecal (IT) administration of rituximab, provided via an Ommaya reservoir, for the treatment of progressive multiple sclerosis (PMS). The objective of this initial study was to monitor B lymphocytes in peripheral blood (PB) and CSF from the first 10 patients 1 year posttreatment.

    Methods: Dose titration was performed with daily escalation from 1 mg to 25 mg IT rituximab (n=3). Lymphocyte subpopulations were monitored daily during dose escalation in PB by flow cytometry and subsequently every 3 months for 1 year, after a total dose of 3 x 25 mg. PB B-lymphocyte subpopulations for the remaining patients (n = 7) were monitored at regular intervals. CSF lymphocyte subpopulations for all patients were monitored by flow cytometry every 2-3 months.

    Results: The PB B-lymphocyte count dropped rapidly after the first 2 injections (total dose of 3.5 mg IT rituximab) to undetectable levels. Three 25-mg doses given once per week depleted peripheral B lymphocytes entirely for the following 3-6 month period.

    Conclusions: Monoclonal antibodies seem to rapidly redistribute to the peripheral compartment following IT injection. Ultra-low doses of rituximab given IT are sufficient to cause complete depletion of peripheral B lymphocytes, indicating that low-dose IT treatment has the potential to be effective in both the CNS and systemic compartments.

    Classification of evidence: This study provides Class IV evidence that for patients with PMS, rituximab provided via an Ommaya reservoir depletes peripheral blood B lymphocytes.

  • 8.
    Svenningsson, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Department of Clinical Sciences, Lund University, Lund, Sweden.
    Salzer, Jonatan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Vågberg, Mattias
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Increasing prevalence of multiple sclerosis in Vasterbotten County of Sweden2015In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 132, no 6, p. 389-394Article in journal (Refereed)
    Abstract [en]

    Objectives To update the incidence and prevalence of multiple sclerosis (MS) in Vasterbotten County, Sweden, and to compare this to previous investigations in the same area. Background Northern Sweden is a high-risk area for developing MS. Vasterbotten County has previously been surveyed in detail regarding the occurrence of MS. In several countries, increases in MS prevalence and incidence as well as a change in the sex ratio have been reported. Materials and methods Multiple sources were used to identify MS cases in Vasterbotten that either had their onset of the disease from 1998 to 2010 and/or lived in Vasterbotten, the two dates chosen for prevalence calculation: the 31st of December 2005 and 2010. Results The mean yearly incidence of MS in Vasterbotten during the entire period 1998-2010 was 6.0/100,000. The female to male ratio was 2.1. The prevalence of MS in Vasterbotten was 188/100,000 on 31st of December 2005 and 215/100,000 on 31st of December 2010. The MS prevalence increased over time from 1990 to 2010. Conclusions The prevalence of MS in Vasterbotten County has increased between 1990 and 2010, while no statistically significant increase in incidence was seen.

  • 9.
    Svenningsson, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Salzer, Jonatan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Vågberg, Mattias
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    MS disease activity in RESTORE: a randomized 24-week natalizumab treatment interruption study2014In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 83, no 22, p. 2099-2100Article in journal (Refereed)
  • 10.
    Vågberg, Mattias
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Brain parenchymal fraction in healthy individuals and in clinical follow-up of multiple sclerosis2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background Multiple sclerosis (MS) is an autoimmune disease characterised by inflammatory damage to the central nervous system (CNS). Accumulated CNS injury can be quantified as brain atrophy, definable as a reduction in brain parenchymal fraction (BPF). BPF correlate with disability in MS and is used routinely as an endpoint in clinical trials. In 2009/2010, a new MS clinical care program, that includes follow-up of BPF, was introduced at Umeå University Hospital (NUS). Levels of neurofilament light polypetide (NFL) and glial fibrillary acidic protein (GFAP) in cerebrospinal fluid (CSF) are markers of axonal and astrocytic injury, respectively, and also potential surrogate biomarkers for BPF decline. The goals of this thesis were to establish age-adjusted values of BPF in healthy individuals and to relate these to the BPF values from individuals with MS as well as to the levels of NFL and GFAP in CSF. Another goal was to investigate if expanded disability status scale (EDSS)-worsening could be predicted in a clinical MS cohort and if BPF measurements could contribute to such predictions. Methods A group of 111 healthy individuals volunteered to participate in the studies. A total of 106 of these underwent MRI with BPF measurements, 53 underwent lumbar puncture (LP) with measurement of NFL and GFAP and 48 underwent both MRI and LP. Three different automatic and one manual method were utilised to determine BPF. A literature search on BPF in healthy individuals was performed for the purpose of a systematic review. For studying disability progression in MS, all individuals with MS followed at NUS and included in the Swedish MS registry were included if they had matched data on BPF, EDSS and lesion load as part of clinical follow-up (n=278). Results BPF as well as NFL and GFAP levels in CSF were all associated with age. NFL was associated with BPF and GFAP, but only the association with GFAP was retained when adjusting for age. Significant differences were found between different methods for BPF determination. In the MS population, BPF was associated with EDSS. Only progressive disease course could predict EDSS worsening. Conclusion The data on BPF and levels of NFL and GFAP in CSF of healthy individuals can aid in the interpretation of these variables in the setting of MS. Knowledge on differences in BPF data from different methods for BPF determination can be useful in comparing data across studies, but also highlights the need for a commonly accepted gold standard. The correlation between GFAP and NFL levels in CSF may indicate an association between glial and axonal turnover that is independent of the aging effect on the brain. However, the low number of volunteers for LP precluded clear conclusions. An association between BPF and EDSS was seen in the MS group. The ability to predict EDSS worsening in the clinical MS cohort was limited.

  • 11.
    Vågberg, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Lindqvist, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Brain parenchymal fraction in an age-stratified healthy population: determined by MRI using manual segmentation and three automated segmentation methods2016In: Journal of neuroradiology, ISSN 0150-9861, E-ISSN 1773-0406, Vol. 43, no 6, p. 384-391Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Brain atrophy is a prominent feature in many neurodegenerative diseases, such as multiple sclerosis, but age-related decrease of brain volume occurs regardless of pathological neurodegeneration. Changes in brain volume can be described by use of the brain parenchymal fraction (BPF), most often defined as the ratio of total brain parenchyma to total intracranial space. The BPF is of interest both in research and in clinical practice. To be able to properly interpret this variable, the normal range of BPF must be known. The objective of this study is to present normal values for BPF, stratified by age, and compare manual BPF measurement to three automated methods. MATERIALS AND METHODS: The BPFs of 106 healthy individuals aged 21 to 85 years were determined by the automated segmentation methods SyMap, VBM8 and SPM12. In a subgroup of 54 randomly selected individuals, the BPF was also determined by manual segmentation. RESULTS: The median (IQR) BPFs of the whole study population were 0.857 (0.064), 0.819 (0.028) and 0.784 (0.073) determined by SyMap, VBM8 and SPM12, respectively. The BPF decreased with increasing age. The correlation coefficients between manual segmentation and SyMap, VBM8 and SPM12 were 0.93 (P<0.001), 0.77 (P<0.001) and 0.56 (P<0.001), respectively. CONCLUSIONS: There was a clear relationship between increasing age and decreasing BPF. Knowledge of the range of normal BPF in relation to age group will help in the interpretation of BPF data. The automated segmentation methods displayed varying degrees of similarity to the manual reference, with SyMap being the most similar.

  • 12.
    Vågberg, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Axelsson, M.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Burman, J.
    Cananau, C.
    Forslin, Y.
    Granberg, T.
    Gunnarsson, M.
    von Heijne, A.
    Jönsson, L.
    Karrenbauer, V. D.
    Larsson, E. -M
    Lindqvist, T.
    Lycke, J.
    Lönn, L.
    Mentesidou, E.
    Müller, S.
    Nilsson, P.
    Piehl, F.
    Svenningsson, A.
    Vrethem, M.
    Wikström, J.
    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 Society2017In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 135, no 1, p. 17-24Article, review/survey (Refereed)
    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.

  • 13.
    Vågberg, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Granåsen, Gabriel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
    Brain parenchymal fraction in healthy adults: a systematic review of the literature2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 1, article id e0170018Article in journal (Refereed)
    Abstract [en]

    Brain atrophy is an important feature of many neurodegenerative disorders. It can be described in terms of change in the brain parenchymal fraction (BPF). In order to interpret the BPF in disease, knowledge on the BPF in healthy individuals is required. The aim of this study was to determine data on the BPF of healthy individuals via a systematic review of the literature. The databases PubMed and Scopus were searched and 95 articles, including a total of 9269 individuals, were identified including the required data. We present values of BPF from healthy individuals stratified by age and post-processing method. The BPF correlated with age and there were significant differences in age-adjusted BPF between methods. This study contributes to increased knowledge on BPF in healthy individuals, which may assist in the interpretation of BPF in the setting of disease. We highlight the differences between post-processing methods and the need for a consensus gold standard. 

  • 14.
    Vågberg, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Granåsen, Gabriel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Svenningsson, Rasmus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Lindqvist, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Prediction of disability increase in a real world multiple sclerosis cohortManuscript (preprint) (Other academic)
    Abstract [en]

    BACKGROUND Multiple sclerosis (MS) is an autoimmune disease characterized by demyelinating CNS-lesions and neurodegeneration. Brain atrophy measurements have been demonstrated to provide prognostic information. Assessment of brain atrophy via magnetic resonance imaging (MRI) using the Brain Parenchymal Fraction (BPF) was added to the clinical follow-up of individuals with MS at Umeå University Hospital in 2009/2010.  

    OBJECTIVE To investigate whether an increase in disability, measured by a short to medium term increase in EDSS, can be predicted using clinically available variables.  To assess if the previously described association between brain atrophy and disability could be detected in the setting of the clinical care program at Umeå University Hospital.

    METHODS All adult MS patients with simultaneous data on BPF, lesion count and EDSS at least at one occasion (n=278) were included. Individuals with two (n=163) and three (n=68) time points with complete data were used for testing the ability to predict Expanded Disability Status Scale (EDSS) score longitudinally.

     RESULTS The EDSS was found to correlate with BPF (p<0.001). Progressive disease course and early EDSS-worsening (SPMS), but no other clinical variables, could predict subsequent EDSS-worsening over follow-up times of approximately 1 to 4 years.

    CONCLUSION BPF was associated with concurrent EDSS, as previously described. Progressive disease course predicted risk for EDSS-increase but it was otherwise very difficult to predict increased disability in this treated MS-cohort. We discuss possible reasons for the lack of predictive value from clinically used variables in a treated MS cohort. 

  • 15.
    Vågberg, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Kumlin, Urban
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Humoral immune response to influenza vaccine in natalizumab-treated MS patients2012In: Neurological Research, ISSN 0161-6412, E-ISSN 1743-1328, Vol. 34, no 7, p. 730-733Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Natalizumab is a drug with documented efficacy in relapsing?remitting multiple sclerosis (RRMS). The mechanism of action of natalizumab has immunosuppressive properties and it is not yet investigated if treatment with natalizumab affects the immunological response to vaccination. This study aims to investigate the humoral immune response to influenza vaccine while undergoing treatment with natalizumab.

    METHODS: A cohort of 17 RRMS patients treated with natalizumab and 10 healthy controls received trivalent influenza A/B vaccine. Influenza-specific immunoglobulin G (IgG) levels were determined at baseline and after 4, 8, and 12 weeks.

    RESULTS: Both groups experienced a significant increase in anti-influenza B IgG after the vaccination. Both groups also experienced a smaller increase in anti-influenza A IgG, but this was only significant for the natalizumab group. The IgG titers compared between the groups did not differ significantly at any of the time points.

    DISCUSSION: These results indicate that vaccination against influenza in patients treated with natalizumab yields a humoral immune response comparable to that achieved in healthy individuals.

  • 16.
    Vågberg, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Lindqvist, T.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Warntjes, J. B. M.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Automated Determination of Brain Parenchymal Fraction in Multiple Sclerosis2013In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 34, no 3, p. 498-504Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Brain atrophy is a manifestation of tissue damage in MS. Reduction in brain parenchymal fraction is an accepted marker of brain atrophy. In this study, the approach of synthetic tissue mapping was applied, in which brain parenchymal fraction was automatically calculated based on absolute quantification of the tissue relaxation rates R1 and R2 and the proton attenuation. MATERIALS AND METHODS: The BPF values of 99 patients with MS and 35 control subjects were determined by using SyMap and tested in relationship to clinical variables. A subset of 5 patients with MS and 5 control subjects were also analyzed with a manual segmentation technique as a reference. Reproducibility of SyMap was assessed in a separate group of 6 healthy subjects, each scanned 6 consecutive times. RESULTS: Patients with MS had significantly lower BPF (0.852 0.0041, mean +/- SE) compared with control subjects (0.890 +/- 0.0040). Significant linear relationships between BPF and age, disease duration, and Expanded Disability Status Scale scores were observed (P < .001). A strong correlation existed between SyMap and the reference method (r = 0.96; P < .001) with no significant difference in mean BPF. Coefficient of variation of repeated SyMap BPF measurements was 0.45%. Scan time was <6 minutes, and postprocessing time was <2 minutes. CONCLUSIONS: SyMap is a valid and reproducible method for determining BPF in MS within a clinically acceptable scan time and postprocessing time. Results are highly congruent with those described using other methods and show high agreement with the manual reference method.

  • 17.
    Vågberg, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Lindqvist, T.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Birgander, R.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Brain parenchymal fraction in the healthy - determined by MRI in an age stratified population and via a systematic review of the literature2014In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, no Supplement 1, p. 259-259Article in journal (Other academic)
  • 18.
    Vågberg, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Norgren, N.
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Levels and age dependency of neurofilament light in healthy individuals and its relation to the brain parenchymal fraction2014In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, no Supplement 1, p. 181-181Article in journal (Other academic)
  • 19.
    Vågberg, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Norgren, Niklas
    UmanDiagnostics AB, Umeå, Sweden.
    Dring, Ann
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Lindqvist, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Zetterberg, Henrik
    Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology, Queen Square, London, United Kingdom.
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Levels and Age Dependency of Neurofilament Light and Glial Fibrillary Acidic Protein in Healthy Individuals and Their Relation to the Brain Parenchymal Fraction2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 8, article id e0135886Article in journal (Refereed)
    Abstract [en]

    Background Neurofilament light (NFL) and Glial Fibrillary Acidic Protein (GFAP) are integral parts of the axonal and astrocytal cytoskeletons respectively and are released into the cerebrospinal fluid (CSF) in cases of cellular damage. In order to interpret the levels of these biomarkers in disease states, knowledge on normal levels in the healthy is required. Another biomarker for neurodegeneration is brain atrophy, commonly measured as brain parenchymal fraction (BPF) using magnetic resonance imaging (MRI). Potential correlations between levels of NFL, GFAP and BPF in healthy individuals have not been investigated. Objectives To present levels of NFL and GFAP in healthy individuals stratified for age, and investigate the correlation between them as well as their correlation with BPF. Methods The CSF was analysed in 53 healthy volunteers aged 21 to 70 (1 sample missing for GFAP analysis) and 48 of the volunteers underwent determination of BPF using MRI. Results Mean (+/- SD) NFL was 355 ng/L (+/- 214), mean GFAP was 421 ng/L (+/- 129) and mean BPF was 0.867 (+/- 0.035). All three biomarkers correlated with age. NFL also correlated with both GFAP and BPF. When controlled for age, only the correlation between NFL and GFAP retained statistical significance. Conclusions This study presents data on age-stratified levels of NFL and GFAP in the CSF of healthy individuals. There is a correlation between levels of NFL and GFAP and both increase with age. A correlation between NFL and BPF was also found, but did not retain statistical significance if controlled for age.

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