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Svenningsson, Anders
Alternative names
Publications (10 of 67) Show all publications
de Flon, P., Laurell, K., Sundström, P., Blennow, K., Söderström, L., Zetterberg, H., . . . Svenningsson, A. (2019). Comparison of plasma and cerebrospinal fluid neurofilament light in a multiple sclerosis trial. Acta Neurologica Scandinavica, 139(5), 462-468
Open this publication in new window or tab >>Comparison of plasma and cerebrospinal fluid neurofilament light in a multiple sclerosis trial
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2019 (English)In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 139, no 5, p. 462-468Article in journal (Refereed) Published
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 and 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 up for 2 years. Thirty patients from the extension trial (STRIX-MS extension), accepting repeated lumbar punctures, were followed up for an additional 3 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 optimize the use in clinical trials.

Keywords
cerebrospinal fluid, clinical trial, multiple sclerosis, neurofilament light, plasma, rituximab, treatment
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-158568 (URN)10.1111/ane.13078 (DOI)000464338600008 ()30740668 (PubMedID)
Available from: 2019-05-27 Created: 2019-05-27 Last updated: 2019-05-27Bibliographically approved
de Flon, P., Söderström, L., Laurell, K., Dring, A., Sundström, P., Gunnarsson, M. & Svenningsson, A. (2018). Immunological profile in cerebrospinal fluid of patients with multiple sclerosis after treatment switch to rituximab and compared with healthy controls. PLoS ONE, 13(2), Article ID e0192516.
Open this publication in new window or tab >>Immunological profile in cerebrospinal fluid of patients with multiple sclerosis after treatment switch to rituximab and compared with healthy controls
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2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 2, article id e0192516Article in journal (Refereed) Published
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.

National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-145871 (URN)10.1371/journal.pone.0192516 (DOI)000424517900086 ()29420590 (PubMedID)
Available from: 2018-03-20 Created: 2018-03-20 Last updated: 2019-05-07Bibliographically approved
Bergman, J., Burman, J., Gilthorpe, J. D., Zetterberg, H., Jiltsova, E., Bergenheim, T. & Svenningsson, A. (2018). Intrathecal treatment trial of rituximab in progressive MS: An open-label phase 1b study. Neurology, 91(20), E1893-E1901
Open this publication in new window or tab >>Intrathecal treatment trial of rituximab in progressive MS: An open-label phase 1b study
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2018 (English)In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 91, no 20, p. E1893-E1901Article in journal (Refereed) Published
Abstract [en]

Objectives To perform a phase 1b assessment of the safety and feasibility of intrathecally delivered rituximab as a treatment for progressive multiple sclerosis (PMS) and to evaluate the effect of treatment on disability and CSF biomarkers during a1-year follow-up period. Methods Three doses of rituximab (25 mg with a 1-week interval) were administered in 23 patients with PMS via a ventricular catheter inserted into the right frontal horn and connected to a subcutaneous Ommaya reservoir. Follow-ups were performed at 1, 3, 6, 9, and 12 months. Results Mild to moderate vertigo and nausea were common but temporary adverse events associated with intrathecal rituximab infusion, which was otherwise well tolerated. The only severe adverse event was a case of low-virulent bacterial meningitis that was treated effectively. Of 7 clinical assessments, only 1 showed statistically significant improvement 1 year after treatment. No treatment effect was observed during the follow-up period among 6 CSF biomarkers. Conclusions Intrathecal administration of rituximab was well tolerated. However, it may involve a risk for injection-related infections. The lack of a control group precludes conclusions being drawn regarding treatment efficacy. ClinicalTrials.gov identifier NCT01719159. Classification of evidence This study provides Class IV evidence that intrathecal rituximab treatment is well tolerated and feasible in PMS but involves a risk of severe infections.

Place, publisher, year, edition, pages
Wolters Kluwer, 2018
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-154850 (URN)10.1212/WNL.0000000000006500 (DOI)000452514700006 ()30305449 (PubMedID)2-s2.0-85056314572 (Scopus ID)
Available from: 2019-01-04 Created: 2019-01-04 Last updated: 2019-05-07Bibliographically approved
Vågberg, M., Granåsen, G. & Svenningsson, A. (2017). Brain parenchymal fraction in healthy adults: a systematic review of the literature. PLoS ONE, 12(1), Article ID e0170018.
Open this publication in new window or tab >>Brain parenchymal fraction in healthy adults: a systematic review of the literature
2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 1, article id e0170018Article in journal (Refereed) Published
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. 

National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-128695 (URN)10.1371/journal.pone.0170018 (DOI)000392372300051 ()28095463 (PubMedID)
Available from: 2016-12-12 Created: 2016-12-12 Last updated: 2018-06-09Bibliographically approved
de Flon, P., Laurell, K., Söderström, L., Gunnarsson, M. & Svenningsson, A. (2017). Improved treatment satisfaction after switching therapy to rituximab in relapsing-remitting MS. Multiple Sclerosis, 23(9), 1249-1257
Open this publication in new window or tab >>Improved treatment satisfaction after switching therapy to rituximab in relapsing-remitting MS
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2017 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 23, no 9, p. 1249-1257Article in journal (Refereed) Published
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.

Keywords
B-cell depletion therapy, Multiple sclerosis, clinical trial, patient-reported outcome measures, rituximab, treatment satisfaction
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-134988 (URN)10.1177/1352458516676643 (DOI)000406386600013 ()27780912 (PubMedID)
Available from: 2017-05-15 Created: 2017-05-15 Last updated: 2018-06-09Bibliographically approved
Vågberg, M., Ambarki, K., Lindqvist, T., Birgander, R. & Svenningsson, A. (2016). Brain parenchymal fraction in an age-stratified healthy population: determined by MRI using manual segmentation and three automated segmentation methods. Journal of neuroradiology, 43(6), 384-391
Open this publication in new window or tab >>Brain parenchymal fraction in an age-stratified healthy population: determined by MRI using manual segmentation and three automated segmentation methods
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2016 (English)In: Journal of neuroradiology, ISSN 0150-9861, E-ISSN 1773-0406, Vol. 43, no 6, p. 384-391Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Masson Editeur, 2016
Keywords
BPF, Brain atrophy, SPM, SyMap, VBM
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-128693 (URN)10.1016/j.neurad.2016.08.002 (DOI)000391158900004 ()27720265 (PubMedID)2-s2.0-84995584817 (Scopus ID)
Available from: 2016-12-12 Created: 2016-12-12 Last updated: 2018-06-09Bibliographically approved
Burman, J. & Svenningsson, A. (2016). Cerebrospinal fluid concentration of Galectin-9 is increased in secondary progressive multiple sclerosis. Journal of Neuroimmunology, 292, 40-44
Open this publication in new window or tab >>Cerebrospinal fluid concentration of Galectin-9 is increased in secondary progressive multiple sclerosis
2016 (English)In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 292, p. 40-44Article in journal (Refereed) Published
Abstract [en]

Galectin-9 is produced by activated astrocytes, induces a pro -inflammatory response in microglia and maybe important to the pathogenesis of secondary progressive MS. In this study, Galectin-9 concentrations in CSF samples from healthy controls and two independent patient cohorts of MS patients were determined by ELISA. Patients from one of the cohorts underwent MRI as well. Galectin-9 concentrations in CSF were higher in SPMS patients than healthy controls and RRMS patients in both cohorts. Galectin-9 concentrations correlated with the number of lesions on Tl-weighted images, but not with gadolinium enhancing lesions, IgG index or CSF cell count.

Keywords
Biomarker, CSF, Multiple sclerosis, Galectin-9
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-119286 (URN)10.1016/j.jneuroim.2016.01.008 (DOI)000372561600006 ()26943957 (PubMedID)
Available from: 2016-05-16 Created: 2016-04-15 Last updated: 2018-06-07Bibliographically approved
de Flon, P., Soderstrom, L., Laurell, K., Gunnarsson, M. & Svenningsson, A. (2016). Changes of cerebrospinal fluid cytokine profile as a result of switching from first line MS-therapies to rituximab. Paper presented at 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), SEP 14-17, 2016, London, ENGLAND. Multiple Sclerosis Journal, 22, 622-622
Open this publication in new window or tab >>Changes of cerebrospinal fluid cytokine profile as a result of switching from first line MS-therapies to rituximab
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2016 (English)In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 22, p. 622-622Article in journal, Meeting abstract (Refereed) Published
Place, publisher, year, edition, pages
SAGE PUBLICATIONS LTD, 2016
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-132860 (URN)000383267202388 ()
Conference
32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), SEP 14-17, 2016, London, ENGLAND
Note

Supplement 3, Meeting Abstract P1189

Available from: 2017-03-23 Created: 2017-03-23 Last updated: 2018-06-09Bibliographically approved
Bergman, J., Dring, A., Wuolikainen, A., Gilthorpe, J., Bergenheim, T. & Svenningsson, A. (2016). Cytokine levels in interstitial brain fluid in progressive multiple sclerosis measured via intracerebral microdialysis. Paper presented at 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), SEP 14-17, 2016, London, ENGLAND. Multiple Sclerosis Journal, 22, 511-511
Open this publication in new window or tab >>Cytokine levels in interstitial brain fluid in progressive multiple sclerosis measured via intracerebral microdialysis
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2016 (English)In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 22, p. 511-511Article in journal, Meeting abstract (Refereed) Published
Place, publisher, year, edition, pages
SAGE PUBLICATIONS LTD, 2016
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-132859 (URN)000383267202206 ()
Conference
32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), SEP 14-17, 2016, London, ENGLAND
Note

Supplement 3, Meeting Abstract P1005

Available from: 2017-03-23 Created: 2017-03-23 Last updated: 2018-06-09Bibliographically approved
Salzer, J., Rajda, C., Sundström, P., Vågberg, M., Vecsei, L. & Svenningsson, A. (2016). How to minimize the risk for headache?: a lumbar puncture practice questionnaire study. IDEGGYOGYASZATI SZEMLE-CLINICAL NEUROSCIENCE, 69(11-12), 397-402
Open this publication in new window or tab >>How to minimize the risk for headache?: a lumbar puncture practice questionnaire study
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2016 (English)In: IDEGGYOGYASZATI SZEMLE-CLINICAL NEUROSCIENCE, ISSN 0019-1442, Vol. 69, no 11-12, p. 397-402Article in journal (Refereed) Published
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.

Keywords
lumbar puncture, LP, questionnaire, AAN guidelines, post lumbar puncture headache
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-131002 (URN)10.18071/isz.69.0397 (DOI)000391162900005 ()
Available from: 2017-02-08 Created: 2017-02-02 Last updated: 2018-06-09Bibliographically approved
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