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BETA
Bergman, Joakim
Alternative names
Publications (7 of 7) Show all publications
Bergman, J., Svenningsson, A., Liv, P. & Burman, J. (2019). Poor correlation between protein levels in different CNS compartments in patients with progressive MS. Paper presented at 35th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) / 24th Annual Conference of Rehabilitation in MS, SEP 11-13, 2019, Stockholm, SWEDEN. Multiple Sclerosis, 25, 432-433
Open this publication in new window or tab >>Poor correlation between protein levels in different CNS compartments in patients with progressive MS
2019 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, p. 432-433Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Sage Publications, 2019
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-164059 (URN)000485303102021 ()
Conference
35th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) / 24th Annual Conference of Rehabilitation in MS, SEP 11-13, 2019, Stockholm, SWEDEN
Note

Supplement: 2 

Special Issue: SI 

Meeting Abstract: P840

Available from: 2019-10-17 Created: 2019-10-17 Last updated: 2019-10-17Bibliographically 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
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
Al Nimer, F., Elliott, C., Bergman, J., Khademi, M., Dring, A. M., Aeinehband, S., . . . Piehl, F. (2016). Lipocalin-2 is increased in progressive multiple sclerosis and inhibits remyelination. Neurology: Neuroimmunology and neuroinflammation, 3(1), Article ID e191.
Open this publication in new window or tab >>Lipocalin-2 is increased in progressive multiple sclerosis and inhibits remyelination
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2016 (English)In: Neurology: Neuroimmunology and neuroinflammation, ISSN 0948-6259, E-ISSN 2332-7812, Vol. 3, no 1, article id e191Article in journal (Refereed) Published
Abstract [en]

Objective: We aimed to examine the regulation of lipocalin-2 (LCN2) in multiple sclerosis (MS) and its potential functional relevance with regard to myelination and neurodegeneration. Methods: We determined LCN2 levels in 3 different studies: (1) in CSF and plasma from a case-control study comparing patients with MS (n = 147) with controls (n = 50) and patients with relapsing-remitting MS (n = 75) with patients with progressive MS (n = 72); (2) in CSF and brain tissue microdialysates from a case series of 7 patients with progressive MS; and (3) in CSF at baseline and 60 weeks after natalizumab treatment in a cohort study of 17 patients with progressive MS. Correlation to neurofilament light, a marker of neuroaxonal injury, was tested. The effect of LCN2 on myelination and neurodegeneration was studied in a rat in vitro neuroglial cell coculture model. Results: Intrathecal production of LCN2 was increased predominantly in patients with progressive MS (p < 0.005 vs relapsing-remitting MS) and displayed a positive correlation to neurofilament light (p = 0.005). Levels of LCN2 in brain microdialysates were severalfold higher than in the CSF, suggesting local production in progressive MS. Treatment with natalizumab in progressive MS reduced LCN2 levels an average of 13% (p < 0.0001). LCN2 was found to inhibit remyelination in a dose-dependent manner in vitro. Conclusions: LCN2 production is predominantly increased in progressive MS. Although this moderate increase does not support the use of LCN2 as a biomarker, the correlation to neurofilament light and the inhibitory effect on remyelination suggest that LCN2 might contribute to neurodegeneration through myelination-dependent pathways.

National Category
Neurology Neurosciences
Identifiers
urn:nbn:se:umu:diva-127257 (URN)10.1212/NXI.0000000000000191 (DOI)000384572500009 ()26770997 (PubMedID)
Available from: 2016-11-10 Created: 2016-11-03 Last updated: 2019-05-06Bibliographically approved
Bergman, J., Dring, A., Zetterberg, H., Blennow, K., Norgren, N., Gilthorpe, J., . . . Svenningsson, A. (2016). Neurofilament light in CSF and serum is a sensitive marker for axonal white matter injury in MS. Neurology: Neuroimmunology and neuroinflammation, 3(5), Article ID e271.
Open this publication in new window or tab >>Neurofilament light in CSF and serum is a sensitive marker for axonal white matter injury in MS
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2016 (English)In: Neurology: Neuroimmunology and neuroinflammation, ISSN 0948-6259, E-ISSN 2332-7812, Vol. 3, no 5, article id e271Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: In an ongoing, open-label, phase 1b study on the intrathecal administration of rituximab for progressive multiple sclerosis, an intraventricular catheter was inserted for drug delivery. The objective of this study was to characterize the limited white matter axonal injury evoked by catheter insertion by analyzing a panel of markers for tissue damage in CSF and serum.

METHODS: Lumbar CSF and serum were collected before catheter insertion and at regular intervals during the follow-up period of 1 year. Levels of neurofilament light polypeptide (NF-L), glial fibrillary acidic protein, microtubule-associated protein tau, and S100 calcium binding protein B were measured in the CSF, and NF-L was also quantified in serum at each time point.

RESULTS: One month after neurosurgical trauma, there was a distinct peak in NF-L concentration in both CSF and serum. In contrast, the biomarkers S100 calcium binding protein B, glial fibrillary acidic protein, and microtubule-associated protein tau did not show any significant changes. NF-L levels in both CSF and serum peaked at 1 month post surgery, returning to baseline after 6 to 9 months. A strong correlation was observed between the concentrations of NF-L in CSF and serum.

CONCLUSIONS: The NF-L level, in CSF and serum, appears to be both a sensitive and specific marker for white matter axonal injury. This makes NF-L a valuable tool with which to evaluate acute white matter axonal damage in a clinical setting. Serum analysis of NF-L may become a convenient way to follow white matter axonal damage longitudinally.

National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-131138 (URN)10.1212/NXI.0000000000000271 (DOI)000391169200012 ()27536708 (PubMedID)
Available from: 2017-02-06 Created: 2017-02-06 Last updated: 2018-06-09Bibliographically approved
de Flon, P., Gunnarsson, M., Laurell, K., Söderström, L., Birgander, R., Lindqvist, T., . . . Svenningsson, A. (2016). Reduced inflammation in relapsing-remitting multiple sclerosis after therapy switch to rituximab. Neurology, 87(2), 141-147
Open this publication in new window or tab >>Reduced inflammation in relapsing-remitting multiple sclerosis after therapy switch to rituximab
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2016 (English)In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 87, no 2, p. 141-147Article in journal (Refereed) Published
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.

National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:umu:diva-127981 (URN)10.1212/WNL.0000000000002832 (DOI)000381470700032 ()27316241 (PubMedID)
Available from: 2016-12-05 Created: 2016-11-21 Last updated: 2018-06-09Bibliographically approved
Svenningsson, A., Bergman, J., Dring, A., Vågberg, M., Birgander, R., Lindqvist, T., . . . Bergenheim, T. (2015). Rapid depletion of B lymphocytes by ultra-low-dose rituximab delivered intrathecally. Neurology: Neuroimmunology and neuroinflammation, 2(2), Article ID e79.
Open this publication in new window or tab >>Rapid depletion of B lymphocytes by ultra-low-dose rituximab delivered intrathecally
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2015 (English)In: Neurology: Neuroimmunology and neuroinflammation, ISSN 0948-6259, E-ISSN 2332-7812, Vol. 2, no 2, article id e79Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2015
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-142801 (URN)10.1212/NXI.0000000000000079 (DOI)000218611600003 ()25745637 (PubMedID)
Available from: 2017-12-20 Created: 2017-12-20 Last updated: 2018-06-09Bibliographically approved
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