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  • 1.
    Alping, P.
    et al.
    Karolinska Inst, Stockholm, Sweden..
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Fink, K.
    Karolinska Inst, Stockholm, Sweden..
    Gunnarsson, M.
    Orebro Univ Hosp, Orebro, Sweden..
    Lycke, J.
    Univ Gothenburg, Gothenburg, Sweden..
    Nilsson, P.
    Lund Univ, Lund, Sweden..
    Salzer, J.
    Umea Univ, Umea, Sweden..
    Vrethem, M.
    Linkoping Univ, Linkoping, Sweden..
    Langer-Gould, A.
    Kaiser Permanente Southern Calif, Pasadena, CA USA..
    Svenningsson, A.
    Karolinska Inst, Stockholm, Sweden..
    Frisell, T.
    Karolinska Inst, Stockholm, Sweden..
    Piehl, F.
    Karolinska Inst, Stockholm, Sweden..
    Baseline characteristics from the COMBAT-MS study: Initial analyses suggest main driver for therapy choice is geographic location2017Inngår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 23, s. 714-714Artikkel i tidsskrift (Annet vitenskapelig)
  • 2.
    Alping, P.
    et al.
    Danderyd Hosp, Karolinska Inst, Clin Neurosci, Stockholm, Sweden..
    Svenningsson, A.
    Danderyd Hosp, Karolinska Inst, Clin Sci, Stockholm, Sweden..
    Salzer, J.
    Umea Univ, Pharmacol & Clin Neurosci, Umea, Sweden..
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi. Uppsala Univ, Neurosci, Uppsala, Sweden..
    Dahle, C.
    Linkoping Univ, Clin & Expt Med, Linkopin, Sweden..
    Fink, K.
    Danderyd Hosp, Karolinska Inst, Clin Neurosci, Stockholm, Sweden..
    Hillert, J.
    Danderyd Hosp, Karolinska Inst, Clin Neurosci, Stockholm, Sweden..
    Lycke, J.
    Univ Gothenburg, Clin Neurosci & Rehabil, Gothenburg, Sweden..
    Landtblom, A-M
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Martin, C.
    Danderyd Hosp, Karolinska Inst, Clin Sci, Stockholm, Sweden..
    Nilsson, P.
    Lund Univ, Neurol, Lund, Sweden..
    Walentin, F.
    Orebro Univ Hosp, Neurol, Orebro, Sweden..
    Olsson, T.
    Danderyd Hosp, Karolinska Inst, Clin Neurosci, Stockholm, Sweden..
    Frisell, T.
    Karolinska Inst, Med Solna, Stockholm, Sweden..
    Piehl, F.
    Danderyd Hosp, Karolinska Inst, Clin Neurosci, Stockholm, Sweden..
    Rituximab in multiple sclerosis; data from the swedish MS registry.2016Inngår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 22, nr suppl. 3, s. 49-49Artikkel i tidsskrift (Fagfellevurdert)
  • 3.
    Alping, Peter
    et al.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Piehl, Fredrik
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden;Stockholm Hlth Serv, Acad Specialist Ctr, Stockholm, Sweden;Karolinska Univ Hosp, Dept Neurol, Stockholm, Sweden.
    Langer-Gould, Annette
    Kaiser Permanente, Southern Calif Permanente Med Grp, Southern Clin & Translat Neurosci, Clin & Translat Neurosci, Pasadena, CA USA;Kaiser Permanente, Southern Calif Permanente Med Grp, Clin & Translat Neurosci, Pasadena, CA USA.
    Frisell, Thomas
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Div, Stockholm, Sweden.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Fink, Katharina
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Fogdell-Hahn, Anna
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Gunnarsson, Martin
    Orebro Univ, Ctr Hlth & Med Psychol, Orebro, Sweden.
    Hillert, Jan
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Kockum, Ingrid
    Stockholm Hlth Serv, Acad Specialist Ctr, Stockholm, Sweden.
    Lycke, Jan
    Univ Gothenburg, Dept Clin Neurosci & Rehabil, Gothenburg, Sweden.
    Nilsson, Petra
    Lund Univ, Dept Clin Sci Neurol, Lund, Sweden.
    Olsson, Tomas
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Salzer, Jonatan
    Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden.
    Svenningsson, Anders
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden.
    Virtanen, Suvi
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Vrethem, Magnus
    Validation of the Swedish Multiple Sclerosis Register: Further Improving a Resource for Pharmacoepidemiologic Evaluations2019Inngår i: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 30, nr 2, s. 230-233Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 4.
    Bergman, Joakim
    et al.
    Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Gilthorpe, Jonathan D.
    Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden.
    Zetterberg, Henrik
    Gothenburg Univ, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Sahlgrenska Acad, Gothenburg, Sweden;Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden;UCL Inst Neurol, Dept Mol Neurosci, Queen Sq, London, England;UCL, UK Dementia Res Inst, London, England.
    Jiltsova, Elena
    Uppsala Univ, Dept Neurosci, Uppsala, Sweden.
    Bergenheim, Tommy
    Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden.
    Svenningsson, Anders
    Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden;Karolinska Inst, Dept Clin Sci, Danderyd Hosp, Stockholm, Sweden.
    Intrathecal treatment trial of rituximab in progressive MS An open-label phase 1b study2018Inngår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 91, nr 20, s. E1893-E1901Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 5.
    Berntsson, Shala G.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Kristoffersson, A
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi. Neurology Policlinic, Department of Medical Specialist, Motala General Hospital, Motala, Sweden.
    Boström, I
    Department of Clinical and Experimental Medicine, Neurology, Medical Faculty, University of Linköping, Linköping, Sweden.
    Feresiadou, Amalia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Landtblom, Anne-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi. Department of Clinical and Experimental Medicine, Neurology, Medical Faculty, University of Linköping, Linköping, Sweden; Neurology Policlinic, Department of Medical Specialist, Motala General Hospital, Motala, Sweden.
    Rapidly increasing off-label use of rituximab in multiple sclerosis in Sweden: Outlier or predecessor?2018Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 138, nr 4, s. 327-331Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: Off-label use of rituximab to treat MS patients in Sweden is high, and the need for long-term safety data may not be met. Our objectives were to assess the rate of rituximab prescription in patients with multiple sclerosis in Sweden and, in addition, to evaluate the safety of rituximab in a single centre for patients with multiple sclerosis.

    MATERIAL AND METHODS: Review of the Swedish MS register was performed to study the number of MS patients treated with rituximab during the last 6 years. Investigation also included a retrospective review of medical files in search for possible side effects/adverse events in all adult patients with MS treated with rituximab at Uppsala University Hospital.

    RESULTS: Presently, in Sweden the rate of rituximab prescriptions in relation to other annually started of disease- modifying drugs in MS is 53.5%.

    CONCLUSIONS: The share of MS patients in Sweden who are treated with rituximab is very high, and also rapidly increasing. Taken into account the off-label use, cases with adverse medical conditions that could possibly be related to rituximab use should be reported thoroughly.

  • 6.
    Bostrom, I.
    et al.
    Linkoping Univ, Linkoping, Sweden..
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Landtblom, A-M
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Adverse events of rituximab in a Swedish MS population sample.2016Inngår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 22, s. 871-871Artikkel i tidsskrift (Fagfellevurdert)
  • 7.
    Bridel, Claire
    et al.
    Vrije Univ Amsterdam Med Ctr, Neurochem Lab, Dept Clin Chem, Neurosci Campus Amsterdam, NL-1081 HV Amsterdam, Netherlands.
    van Wieringen, Wessel N.
    Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands;Vrije Univ Amsterdam, Dept Math, Amsterdam, Netherlands.
    Zetterberg, Henrik
    Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden;Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Sahlgrenska Acad, Gothenburg, Sweden;UCL Inst Neurol, Dept Mol Neurosci, Queen Sq, London, England;UCL, Dementia Res Inst, London, England.
    Tijms, Betty M.
    Vrije Univ Amsterdam Med Ctr, Dept Neurol, Neurosci Campus Amsterdam, Amsterdam, Netherlands;Vrije Univ Amsterdam Med Ctr, Alzheimer Ctr, Neurosci Campus Amsterdam, Amsterdam, Netherlands.
    Teunissen, Charlotte E.
    Vrije Univ Amsterdam Med Ctr, Neurochem Lab, Dept Clin Chem, Neurosci Campus Amsterdam, NL-1081 HV Amsterdam, Netherlands.
    Alvarez-Cermeno, Jose C.
    Ramon y Cajal Univ Hosp, Multiple Sclerosis Unit, Madrid, Spain.
    Andreasson, Ulf
    Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden.
    Axelsson, Markus
    Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Sahlgrenska Acad, Gothenburg, Sweden.
    Backstrom, David C.
    Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden.
    Bartos, Ales
    Charles Univ Prague, Dept Neurol, Fac Med 3, Prague, Czech Republic;Gen Univ Hosp, Prague, Czech Republic;Natl Inst Mental Hlth, Klecany, Czech Republic.
    Bjerke, Maria
    Univ Antwerp, Dept Biomed Sci, Reference Ctr Biol Markers Dementia BIODEM, Inst Born Bunge, Antwerp, Belgium.
    Blennow, Kaj
    Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden;Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Sahlgrenska Acad, Gothenburg, Sweden.
    Boxer, Adam
    Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA.
    Brundin, Lou
    Karolinska Inst, Neuroimmunol Unit, Dept Clin Neurosci, Stockholm, Sweden;Karolinska Univ Hosp, Dept Neurol, Stockholm, Sweden.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Landtblom: Neurologi.
    Christensen, Tove
    Aarhus Univ, Dept Biomed, Aarhus, Denmark;Rigshosp, Dept Neurol, Copenhagen Univ Hosp, Copenhagen, Denmark.
    Fialova, Lenka
    Gen Univ Hosp, Prague, Czech Republic;First Fac Med, Inst Med Biochem, Prague, Czech Republic;Charles Univ Prague, Diagnost Lab, Prague, Czech Republic.
    Forsgren, Lars
    Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden.
    Frederiksen, Jette L.
    Rigshosp, Dept Neurol, Copenhagen Univ Hosp, Copenhagen, Denmark.
    Gisslen, Magnus
    Univ Gothenburg, Sahlgrenska Acad, Dept Infect Dis, Gothenburg, Sweden.
    Gray, Elizabeth
    Univ Oxford, Nuffield Dept Clin Neurosci, Oxford, England.
    Gunnarsson, Martin
    Orebro Univ Hosp, Dept Neurol, Fac Med & Hlth, Orebro, Sweden.
    Hall, Sara
    Lund Univ, Clin Memory Res Unit, Dept Clin Sci, Fac Med, Lund, Sweden;Lund Univ, Wallenberg Ctr Mol Med, Lund, Sweden.
    Hansson, Oskar
    Lund Univ, Clin Memory Res Unit, Dept Clin Sci, Fac Med, Lund, Sweden;Lund Univ, Wallenberg Ctr Mol Med, Lund, Sweden.
    Herbert, Megan K.
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Inst Med, Gothenburg, Sweden;Sahlgrens Univ Hosp, Dept Endocrinol, Gothenburg, Sweden.
    Jakobsson, Joel
    Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Sahlgrenska Acad, Gothenburg, Sweden.
    Jessen-Krut, Jan
    Univ Gothenburg, Sahlgrenska Acad, Dept Infect Dis, Gothenburg, Sweden.
    Janelidze, Shorena
    Lund Univ, Clin Memory Res Unit, Dept Clin Sci, Fac Med, Lund, Sweden;Lund Univ, Wallenberg Ctr Mol Med, Lund, Sweden.
    Johannsson, Gudmundur
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Inst Med, Gothenburg, Sweden;Sahlgrens Univ Hosp, Dept Endocrinol, Gothenburg, Sweden.
    Jonsson, Michael
    Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Sahlgrenska Acad, Gothenburg, Sweden.
    Kappos, Ludwig
    Univ Hosp, Dept Med, Basel, Switzerland;Univ Basel, Basel, Switzerland.
    Khademi, Mohsen
    Karolinska Inst, Neuroimmunol Unit, Dept Clin Neurosci, Stockholm, Sweden;Karolinska Univ Hosp, Dept Neurol, Stockholm, Sweden.
    Khalil, Michael
    Med Univ Graz, Dept Neurol, Graz, Austria.
    Kuhle, Jens
    Univ Hosp, Dept Med, Basel, Switzerland;Univ Basel, Basel, Switzerland.
    Landen, Mikael
    Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Sahlgrenska Acad, Gothenburg, Sweden.
    Leinonen, Ville
    Univ Eastern Finland, Inst Clin Med, Neurosurg, Kuopio, Finland;Kuopio Univ Hosp, Dept Neurosurg, Kuopio, Finland.
    Logroscino, Giancarlo
    Univ Bari, Unit Neurodegenerat Dis, Dept Clin Res Neurol, Bari, Italy.
    Lu, Ching-Hua
    Blizard, North East London & Essex MND Care Ctr, Neurosci & Trauma Ctr, London, England;China Med Univ Hosp, Dept Neurol, Taichung, Taiwan.
    Lycke, Jan
    Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Sahlgrenska Acad, Gothenburg, Sweden.
    Magdalinou, Nadia K.
    UCL Inst Neurol, Reta Lila Weston Inst Neurol Studies, Queen Sq, London, England.
    Malaspina, Andrea
    Blizard, North East London & Essex MND Care Ctr, Neurosci & Trauma Ctr, London, England;Barts, Inst Cell & Mol Med, London, England;Barts, London Sch Med & Dent, London, England;Barts, Barts Hlth NHS Trust, London, England.
    Mattsson, Niklas
    Lund Univ, Clin Memory Res Unit, Dept Clin Sci, Fac Med, Lund, Sweden;Lund Univ, Wallenberg Ctr Mol Med, Lund, Sweden.
    Meeter, Lieke H.
    Erasmus MC, Alzheimer Ctr, Rotterdam, Netherlands;Erasmus MC, Dept Neurol, Rotterdam, Netherlands;Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Amsterdam, Netherlands.
    Mehta, Sanjay R.
    Univ Calif San Diego, Div Infect Dis, La Jolla, CA 92093 USA.
    Modvig, Signe
    Rigshosp, Dept Clin Immunol, Copenhagen Univ Hosp, Copenhagen, Denmark.
    Olsson, Tomas
    Karolinska Inst, Neuroimmunol Unit, Dept Clin Neurosci, Stockholm, Sweden;Karolinska Univ Hosp, Dept Neurol, Stockholm, Sweden.
    Paterson, Ross W.
    UCL Inst Neurol, Dementia Res Ctr, Queen Sq, London, England.
    Perez-Santiago, Josue
    Univ Puerto Rico, Puerto Rico OMICS Ctr, Ctr Comprehens Canc, San Juan, PR 00936 USA.
    Piehl, Fredrik
    Karolinska Inst, Neuroimmunol Unit, Dept Clin Neurosci, Stockholm, Sweden;Karolinska Univ Hosp, Dept Neurol, Stockholm, Sweden.
    Pijnenburg, Yolande A. L.
    Vrije Univ Amsterdam Med Ctr, Dept Neurol, Neurosci Campus Amsterdam, Amsterdam, Netherlands;Vrije Univ Amsterdam Med Ctr, Alzheimer Ctr, Neurosci Campus Amsterdam, Amsterdam, Netherlands.
    Pyykko, Okko T.
    Univ Eastern Finland, Inst Clin Med, Neurosurg, Kuopio, Finland;Kuopio Univ Hosp, Dept Neurosurg, Kuopio, Finland.
    Ragnarsson, Oskar
    Orebro Univ Hosp, Dept Neurol, Fac Med & Hlth, Orebro, Sweden.
    Rojas, Julio C.
    Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA.
    Christensen, Jeppe Romme
    Aarhus Univ, Dept Biomed, Aarhus, Denmark;Rigshosp, Dept Neurol, Copenhagen Univ Hosp, Copenhagen, Denmark.
    Sandberg, Linda
    Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden.
    Scherling, Carole S.
    Belmont Univ, Dept Psychol Sci, Nashville, TN USA;Belmont Univ, Neurosci Program, Nashville, TN USA.
    Schott, Jonathan M.
    UCL Inst Neurol, Dementia Res Ctr, Queen Sq, London, England.
    Sellebjerg, Finn T.
    Rigshosp, Dept Neurol, Copenhagen Univ Hosp, Copenhagen, Denmark.
    Simone, Isabella L.
    Univ Bari, Dept Basic Med Sci Neurosci & Sense Organs, Bari, Italy;San Camillo Forlanini Hosp, Rome, Italy.
    Skillback, Tobias
    Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Sahlgrenska Acad, Gothenburg, Sweden.
    Stilund, Morten
    Aarhus Univ, Dept Biomed, Aarhus, Denmark.
    Sundstrom, Peter
    Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden.
    Svenningsson, Anders
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Tortelli, Rosanna
    Univ Bari, Unit Neurodegenerat Dis, Dept Clin Res Neurol, Bari, Italy;Pia Fdn Cardinale G Panico, Lecce, Italy.
    Tortorella, Carla
    Univ Bari, Dept Basic Med Sci Neurosci & Sense Organs, Bari, Italy.
    Trentini, Alessandro
    Univ Ferrara, Dept Biomed & Specialist Surg Sci, Ferrara, Italy.
    Troiano, Maria
    Univ Bari, Dept Basic Med Sci Neurosci & Sense Organs, Bari, Italy.
    Turner, Martin R.
    Univ Oxford, Nuffield Dept Clin Neurosci, Oxford, England.
    van Swieten, John C.
    Erasmus MC, Alzheimer Ctr, Rotterdam, Netherlands;Erasmus MC, Dept Neurol, Rotterdam, Netherlands.
    Vagberg, Mattias
    Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden.
    Verbeek, Marcel M.
    Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Neurol, Nijmegen, Netherlands;Radboud Alzheimer Ctr, Dept Lab Med, Nijmegen, Netherlands.
    Villar, Luisa M.
    Ramon y Cajal Univ Hosp, Dept Immunol, Madrid, Spain.
    Visser, Pieter Jelle
    Vrije Univ Amsterdam Med Ctr, Dept Neurol, Neurosci Campus Amsterdam, Amsterdam, Netherlands;Vrije Univ Amsterdam Med Ctr, Alzheimer Ctr, Neurosci Campus Amsterdam, Amsterdam, Netherlands;Maastricht Univ, Dept Psychiat & Neuropsychol, Sch Mental Hlth & Neurosci, Alzheimer Ctr Limburg, Maastricht, Netherlands.
    Wallin, Anders
    Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Sahlgrenska Acad, Gothenburg, Sweden.
    Weiss, Andreas
    Evotec AG, Manfred Eigen Campus, Hamburg, Germany.
    Wikkelso, Carsten
    Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Sahlgrenska Acad, Gothenburg, Sweden.
    Wild, Edward J.
    UCL Inst Neurol, Queen Sq, London, England.
    Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology: A Systematic Review and Meta-analysis2019Inngår i: JAMA Neurology, ISSN 2168-6149, E-ISSN 2168-6157, Vol. 76, nr 9, s. 1035-1048Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    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 10 059 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.

  • 8.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Curing Multiple Sclerosis: How to do it and how to prove it2014Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for multiple sclerosis (MS) with now more than 600 documented cases in the medical literature. Long-term remission can be achieved with this therapy, but when is it justified to claim that a patient is cured from MS? In attempt to answer this question, the outcome of the Swedish patients is described, mechanisms behind the therapeutic effect are discussed and new tools for demonstration of absence of disease have been developed.

    In Swedish patients treated with HSCT for aggressive MS, disease free survival was 68 % at five years, and no patient progressed after three years of stable disease. Presence of gadolinium enhancing lesions prior to HSCT was associated with a favorable outcome (disease free survival 79 % vs 46 %, p=0.028). There was no mortality and no patient required intensive care.

    The immune system of twelve of these patients was investigated further. In most respects HSCT-treated patients were similar to healthy controls, demonstrating normalization. In the presence of a potential antigen, leukocytes from HSCT-treated patients ceased producing pro-inflammatory IL-17 and increased production of the inhibitory cytokine TGF-β1 suggesting restoration of tolerance.

    Cytokine levels and biomarkers of tissue damage were investigated in cerebrospinal fluid from a cohort of MS patients. The levels were related to clinical and imaging findings. A cytokine signature of patients with relapsing-remitting MS could be identified, characterized by increased levels of CCL22, CXCL10, sCD40L, CXCL1 and CCL5 as well as down-regulation of CCL2. Further, we could demonstrate that active inflammation in relapsing-remitting MS is a tissue damaging process, with increased levels of myelin basic protein and neurofilament light. Importantly, relapsing-remitting MS patients in remission displayed no tissue damage. In secondary progressive MS, moderate tissue damage was present without signs of active inflammation.

    From a clinical vantage point, it seems that we confidently can claim cure of relapsing-remitting MS patients after five years absence of disease activity. The new tools for evaluation of disease can strengthen this assertion and may enable earlier prediction of outcome.

    Delarbeid
    1. Autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: the Swedish experience
    Åpne denne publikasjonen i ny fane eller vindu >>Autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: the Swedish experience
    Vise andre…
    2014 (engelsk)Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 85, nr 10, s. 1116-1121Artikkel i tidsskrift (Fagfellevurdert) Published
    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.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-223632 (URN)10.1136/jnnp-2013-307207 (DOI)000344456000228 ()24554104 (PubMedID)
    Tilgjengelig fra: 2014-04-23 Laget: 2014-04-23 Sist oppdatert: 2017-12-05bibliografisk kontrollert
    2. T-cell responses after haematopoietic stem cell transplantation for aggressive relapsing-remitting multiple sclerosis
    Åpne denne publikasjonen i ny fane eller vindu >>T-cell responses after haematopoietic stem cell transplantation for aggressive relapsing-remitting multiple sclerosis
    Vise andre…
    2013 (engelsk)Inngår i: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 140, nr 2, s. 211-219Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Autologous haematopoietic stem cell transplantation (HSCT) for relapsing-remitting multiple sclerosis is a potentially curative treatment, which can give rise to long-term disease remission. However, the mode of action is not yet fully understood. The aim of the study was to evaluate similarities and differences of the CD4(+) T-cell populations between HSCT-treated patients (n = 12) and healthy controls (n = 9). Phenotyping of memory T cells, regulatory T (Treg) cells and T helper type 1 (Th1) and type 17 (Th17) cells was performed. Further, T-cell reactivity to a tentative antigen, myelin oligodendrocyte glycoprotein, was investigated in these patient populations. Patients treated with natalizumab (n = 15) were included as a comparative group. White blood cells were analysed with flow cytometry and T-cell culture supernatants were analysed with magnetic bead panel immunoassays. HSCT-treated patients had similar levels of Treg cells and of Th1 and Th17 cells as healthy subjects, whereas natalizumab-treated patients had lower frequencies of Treg cells, and higher frequencies of Th1 and Th17 cells. Cells from HSCT-treated patients cultured with overlapping peptides from myelin oligodendrocyte glycoprotein produced more transforming growth factor-beta(1) than natalizumab-treated patients, which suggests a suppressive response. Conversely, T cells from natalizumab-treated patients cultured with those peptides produced more interleukin-17 (IL-17), IL-1 and IL-10, indicating a Th17 response. In conclusion, we demonstrate circumstantial evidence for the removal of autoreactive T-cell clones as well as development of tolerance after HSCT. These results parallel the long-term disease remission seen after HSCT.

    Emneord
    haematopoietic stem cell transplantation, multiple sclerosis, natalizumab, neuroimmunology
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-211463 (URN)10.1111/imm.12129 (DOI)000324303200007 ()
    Tilgjengelig fra: 2013-11-25 Laget: 2013-11-25 Sist oppdatert: 2017-12-06bibliografisk kontrollert
    3. The cerebrospinal fluid cytokine signature of multiple sclerosis: a homogenous response that does not conform to the Th1/Th2/Th17 convention
    Åpne denne publikasjonen i ny fane eller vindu >>The cerebrospinal fluid cytokine signature of multiple sclerosis: a homogenous response that does not conform to the Th1/Th2/Th17 convention
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    In this cross-sectional study, we wanted to identify key cytokines characteristic of different stages of multiple sclerosis (MS) that could be used as an outcome measure in clinical trials. To this end, cerebrospinal fluid from a cohort of patients with relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) was investigated with a multiplexed fluorescent bead-based immunoassay. In total 43 cytokines were assessed and related to clinical and imaging data. Cerebrospinal fluid from a separate confirmatory cohort was used to validate cytokines pertinent to SPMS. Increased levels of CCL22, CXCL10 and sCD40L characterized RRMS patients with presence of gadolinium-enhancing lesions; decreased CCL2 and increased CXCL1 and CCL5 were typical of RRMS patients irrespectively of presence of gadolinium-enhancing lesions. IL-15 and IL-27 were increased in SPMS patients, but non-significantly in the confirmation cohort. These homogenous patterns of cytokine activation do not conform to conventional Th1/Th2/Th17 responses.

    Emneord
    cerebrospinal fluid, cytokines, magnetic resonance imaging, multiple sclerosis
    HSV kategori
    Forskningsprogram
    Neurologi
    Identifikatorer
    urn:nbn:se:uu:diva-223241 (URN)
    Tilgjengelig fra: 2014-04-16 Laget: 2014-04-16 Sist oppdatert: 2014-06-30
    4. Assessing tissue damage in multiple sclerosis: a biomarker approach
    Åpne denne publikasjonen i ny fane eller vindu >>Assessing tissue damage in multiple sclerosis: a biomarker approach
    Vise andre…
    2014 (engelsk)Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 130, nr 2, s. 81-89Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    OBJECTIVES:

    Magnetic resonance imaging (MRI) of the brain and spinal cord is the gold standard for assessing disease activity in multiple sclerosis (MS). MRI is an excellent instrument for determination of accumulated damage to the brain and spinal cord, but tells us little about ongoing tissue damage. In this study, biomarkers of oligodendrocyte, axonal and astrocyte injury were related to MRI and clinical findings and used to assess tissue damage in MS.

    MATERIALS AND METHODS:

    Cerebrospinal fluid from 44 patients with relapsing-remitting MS, 20 with secondary progressive MS and 15 controls were investigated with ELISA to determine levels of myelin basic protein (MBP), neurofilament light (NFL) and glial fibrillary acidic protein (GFAp). Patients underwent MRI of the brain and spinal cord, and gadolinium enhancing lesions, T1 lesions and T2 lesions were counted.

    RESULTS:

    Patients in clinical relapse and patients with nonsymptomatic gadolinium enhancing lesions had high levels of MBP and NFL, indicating ongoing damage to oligodendrocytes and axons. The level of MBP dropped quickly within a week from the onset of a relapse, whereas NFL remained elevated for several weeks and GFAp slowly rose during the course of a relapse. Relapsing-remitting MS patients without gadolinium enhancing lesions had values of MBP, NFL and GFAp similar to controls, while patients with secondary progressive disease had moderately increased values of all biomarkers.

    CONCLUSIONS:

    Analysis of MBP, NFL and GFAp provides direct means to measure tissue damage and is a useful addition to our methods for evaluation of MS.

    HSV kategori
    Forskningsprogram
    Klinisk immunologi
    Identifikatorer
    urn:nbn:se:uu:diva-219571 (URN)10.1111/ane.12239 (DOI)000339951900006 ()24571714 (PubMedID)
    Tilgjengelig fra: 2014-03-04 Laget: 2014-03-04 Sist oppdatert: 2018-01-11bibliografisk kontrollert
  • 9.
    Burman, Joachim
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Fox, Robert J.
    Cleveland Clin, Neurol Inst, Mellen Ctr Multiple Sclerosis, Cleveland, OH 44106 USA..
    Autologous hematopoietic stem cell transplantation for MS: Safer than previously thought2017Inngår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 88, nr 22, s. 2072-2073Artikkel i tidsskrift (Annet vitenskapelig)
  • 10.
    Burman, Joachim
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Fransson, Moa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Tötterman, Thomas H.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Fagius, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Mangsbo, Sara M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Loskog, Angelica S. I.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    T-cell responses after haematopoietic stem cell transplantation for aggressive relapsing-remitting multiple sclerosis2013Inngår i: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 140, nr 2, s. 211-219Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Autologous haematopoietic stem cell transplantation (HSCT) for relapsing-remitting multiple sclerosis is a potentially curative treatment, which can give rise to long-term disease remission. However, the mode of action is not yet fully understood. The aim of the study was to evaluate similarities and differences of the CD4(+) T-cell populations between HSCT-treated patients (n = 12) and healthy controls (n = 9). Phenotyping of memory T cells, regulatory T (Treg) cells and T helper type 1 (Th1) and type 17 (Th17) cells was performed. Further, T-cell reactivity to a tentative antigen, myelin oligodendrocyte glycoprotein, was investigated in these patient populations. Patients treated with natalizumab (n = 15) were included as a comparative group. White blood cells were analysed with flow cytometry and T-cell culture supernatants were analysed with magnetic bead panel immunoassays. HSCT-treated patients had similar levels of Treg cells and of Th1 and Th17 cells as healthy subjects, whereas natalizumab-treated patients had lower frequencies of Treg cells, and higher frequencies of Th1 and Th17 cells. Cells from HSCT-treated patients cultured with overlapping peptides from myelin oligodendrocyte glycoprotein produced more transforming growth factor-beta(1) than natalizumab-treated patients, which suggests a suppressive response. Conversely, T cells from natalizumab-treated patients cultured with those peptides produced more interleukin-17 (IL-17), IL-1 and IL-10, indicating a Th17 response. In conclusion, we demonstrate circumstantial evidence for the removal of autoreactive T-cell clones as well as development of tolerance after HSCT. These results parallel the long-term disease remission seen after HSCT.

  • 11.
    Burman, Joachim
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Iacobaeus, Ellen
    Svenningsson, Anders
    Lycke, Jan
    Gunnarsson, Martin
    Nilsson, Petra
    Vrethem, Magnus
    Fredrikson, Sten
    Martin, Claes
    Sandstedt, Anna
    Uggla, Bertil
    Lenhoff, Stig
    Johansson, Jan-Erik
    Isaksson, Cecilia
    Hägglund, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Carlson, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Fagius, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: the Swedish experience2014Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 85, nr 10, s. 1116-1121Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 12.
    Burman, Joachim
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Kirgizov, K
    Russian Childrens Res Hosp, BMT Dept, Moscow, Russia.
    Carlson, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Badoglio, M
    Hop St Antoine, EBMT Paris Study Off, Paris, France.
    Mancardi, G L
    Univ Genoa, Dept Neurosci, Genoa, Italy.
    De Luca, G
    Univ G dAnnunzio, Multiple Sclerosis Ctr, Neurol Clin, Chieti, Italy.
    Casanova, B
    Hosp Univ & Politecninc La Fe, Neuroimmunol Unit, Valencia, Spain.
    Ouyang, J
    Nanjing Univ, Dept Hematol, Affiliated Drum Tower Hosp, Med Sch, Nanjing, Jiangsu, Peoples R China.
    Bembeeva, R
    Pirogov Russian Natl Res Med Univ, Neurosurg & Genet Pediat Fac, Dept Neurol, Moscow, Russia.
    Haas, J
    Jud Krankenhaus, Berlin, Germany.
    Bader, P
    GW Goethe Univ Hosp, Dept Children & Adolescents, Div Stem Cell Transplantat & Immunol, Frankfurt, Germany.
    Snowden, J
    Sheffield Teaching Hosp NHS Fdn Trust, Dept Haematol, Sheffield, S Yorkshire, England; Univ Sheffield, Sheffield, S Yorkshire, England.
    Farge, D
    Paris 7 Univ, INSERM U1160, Paris, France; Paris7 Denis Diderot Univ, St Louis Hosp, AP HP,UF 04, Unite Med Interne Malad Autoimmunes & Pathol Vasc, Paris, France.
    Autologous hematopoietic stem cell transplantation for pediatric multiple sclerosis: a registry-based study of the Autoimmune Diseases Working Party (ADWP) and Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT)2017Inngår i: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 52, nr 8, s. 1133-1137Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Autologous hematopoietic stem cell transplantation (aHSCT) is a promising therapy for multiple sclerosis (MS), which has mainly been used in adults. The purpose of this study was to investigate efficacy and adverse events of aHSCT in the treatment of children with MS using data from the European Society for Blood and Marrow Transplantation registry. Twenty-one patients with a median follow-up time of 2.8 years could be identified. PFS at 3 years was 100%, 16 patients improved in expanded disability status scale score and only 2 patients experienced a clinical relapse. The procedure was generally well tolerated and only two instances of severe transplant-related toxicity were recorded. There was no treatment-related mortality, although one patient needed intensive care. aHSCT may be a therapeutic option for children with disease that does not respond to standard care.

  • 13.
    Burman, Joachim
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi. Univ Uppsala Hosp, Dept Neurol, SE-75185 Uppsala, Sweden.
    Raininko, Raili
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Blennow, Kaj
    Zetterberg, Henrik
    Axelsson, Markus
    Malmeström, Clas
    YKL-40 is a CSF biomarker of intrathecal inflammation in secondary progressive multiple sclerosis.2016Inngår i: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 292, s. 52-57Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    YKL-40 (CHI3L1) is a glycoprotein predominantly produced by reactive astrocytes in chronic active MS lesions, which are common in secondary progressive MS. In this study, YKL-40 was investigated in different stages of MS and in relation to MRI findings. YKL-40 levels in CSF samples from two independent patient cohorts of MS patients were determined with ELISA. CSF YKL-40 was increased in patients with active relapsing-remitting MS and correlated with the number of gadolinium enhancing lesions. Patients with secondary progressive MS had similar high levels of YKL-40, whereas not active relapsing-remitting MS patients had YKL-40 levels comparable to healthy controls.

  • 14.
    Burman, Joachim
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi. Univ Uppsala Hosp, Dept Neurol, SE-75185 Uppsala, Sweden.
    Svenningsson, Anders
    Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden; Univ Hosp Northern Sweden, Umea, Sweden; Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Cerebrospinal fluid concentration of Galectin-9 is increased in secondary progressive multiple sclerosis.2016Inngår i: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 292, s. 40-44Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Galectin-9 is produced by activated astrocytes, induces a pro-inflammatory response in microglia and may be 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 T1-weighted images, but not with gadolinium enhancing lesions, IgG index or CSF cell count.

  • 15.
    Burman, Joachim
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Svensson, Emma
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Fransson, Moa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Loskog, Angelica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Mangsbo, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Tim-3 and PD-1: Regulators of adaptive immunity in multiple sclerosis2014Inngår i: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 275, nr 1-2, s. 141-141Artikkel i tidsskrift (Annet vitenskapelig)
  • 16.
    Burman, Joachim
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Svensson, Emma
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Fransson, Moa
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Loskog, Angelica S I
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Zetterberg, Henrik
    Raininko, Raili
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Svenningsson, Anders
    Fagius, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Mangsbo, Sara M
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    The cerebrospinal fluid cytokine signature of multiple sclerosis: A homogenous response that does not conform to the Th1/Th2/Th17 convention2014Inngår i: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 277, nr 1-2, s. 153-159Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In this cross-sectional study, we wanted to identify key cytokines characteristic of different stages of multiple sclerosis (MS). To this end, cerebrospinal fluid from patients with MS was investigated with a multiplexed fluorescent bead-based immunoassay. In total 43 cytokines were assessed and related to clinical and imaging data. Increased levels of CCL22, CXCL10 and sCD40L characterized relapsing-remitting MS patients with the presence of gadolinium-enhancing lesions; decreased CCL2 and increased CXCL1 and CCL5 were typical of relapsing-remitting MS patients irrespectively of the presence of gadolinium-enhancing lesions. These homogenous patterns of cytokine activation do not conform to conventional Th1/Th2/Th17 responses.

  • 17.
    Burman, Joachim
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Svensson, Emma
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Fransson, Moa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Loskog, Angelica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Zetterberg, Henrik
    Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden..
    Raininko, Raili
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Svenningsson, Anders
    Department of Pharmacology and Clinical Neuroscience, Umeå University and University Hospital of Northern Sweden, Umeå, Sweden..
    Fagius, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Mangsbo, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    The cerebrospinal fluid cytokine signature of multiple sclerosis: a homogenous response that does not conform to the Th1/Th2/Th17 conventionManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    In this cross-sectional study, we wanted to identify key cytokines characteristic of different stages of multiple sclerosis (MS) that could be used as an outcome measure in clinical trials. To this end, cerebrospinal fluid from a cohort of patients with relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) was investigated with a multiplexed fluorescent bead-based immunoassay. In total 43 cytokines were assessed and related to clinical and imaging data. Cerebrospinal fluid from a separate confirmatory cohort was used to validate cytokines pertinent to SPMS. Increased levels of CCL22, CXCL10 and sCD40L characterized RRMS patients with presence of gadolinium-enhancing lesions; decreased CCL2 and increased CXCL1 and CCL5 were typical of RRMS patients irrespectively of presence of gadolinium-enhancing lesions. IL-15 and IL-27 were increased in SPMS patients, but non-significantly in the confirmation cohort. These homogenous patterns of cytokine activation do not conform to conventional Th1/Th2/Th17 responses.

  • 18.
    Burman, Joachim
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Tolf, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Hägglund, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Askmark, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Autologous haematopoietic stem cell transplantation for neurological diseases2018Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 89, nr 2, s. 147-155Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Neuroinflammatory diseases such as multiple sclerosis, neuromyelitis optica, chronic inflammatory demyelinating polyneuropathy and myasthenia gravis are leading causes of physical disability in people of working age. In the last decades significant therapeutic advances have been made that can ameliorate the disease course. Nevertheless, many affected will continue to deteriorate despite treatment, and the costs associated with disease-modifying drugs constitute a significant fiscal burden on healthcare in developed countries. Autologous haematopoietic stem cell transplantation is a treatment approach that aims to ameliorate and to terminate disease activity. The erroneous immune system is eradicated using cytotoxic drugs, and with the aid of haematopoietic stem cells a new immune system is rebuilt. As of today, more than 1000 patients with multiple sclerosis have been treated with this procedure. Available data suggest that autologous haematopoietic stem cell transplantation is superior to conventional treatment in terms of efficacy with an acceptable safety profile. A smaller number of patients with other neuroinflammatory conditions have been treated with promising results. Herein, current data on clinical effect and safety of autologous haematopoietic stem cell transplantation for neurological disease are reviewed.

  • 19.
    Burman, Joachim
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Zelano, Johan
    University of Gothenburg, Sahlgrenska Academy, Department of Clinical Neuroscience, Gothenburg.; Sahlgrenska University Hospital, Gothenburg.
    Epilepsy in multiple sclerosis: A nationwide population-based register study.2017Inngår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 89, nr 24, s. 2462-2468Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To determine the cumulative incidence of epilepsy in a population-based cohort of patients with multiple sclerosis (MS) and to investigate the association between epilepsy and clinical features of MS.

    Methods: All available patients in the Swedish MS register (n = 14,545) and 3 age- and sex-matched controls per patient randomly selected from the population register (n = 43,635) were included. Data on clinical features of MS were retrieved from the Swedish MS register, and data on epilepsy and death were retrieved from comprehensive patient registers.

    Results: The cumulative incidence of epilepsy was 3.5% (95% confidence interval [CI] 3.17–3.76) in patients with MS and 1.4% (95% CI 1.30–1.52) in controls (risk ratio 2.5, 95% CI 2.19–2.76). In a Cox proportional model, MS increased the risk of epilepsy (hazard ratio 3.2, 95% CI 2.64–3.94). Patients with relapsing-remitting MS had a cumulative incidence of epilepsy of 2.2% (95% CI 1.88–2.50), whereas patients with progressive disease had a cumulative incidence of 5.5% (95% CI 4.89–6.09). The cumulative incidence rose continuously with increasing disease duration to 5.9% (95% CI 4.90–7.20) in patients with disease duration ≥34 years. Patients with an Expanded Disability Status Scale (EDSS) score ≥7 had a cumulative incidence of epilepsy of 5.3% (95% CI 3.95–7.00). Disease duration and EDSS score were associated with epilepsy after multiple logistic regression (odds ratio [OR] 1.03, 95% CI 1.01–1.04 per year, p = 0.001; and OR 1.2, 95% CI 1.09–1.26 per EDSS step, p < 0.0001).

    Conclusions: Epilepsy is more common among patients with MS than in the general population, and a diagnosis of MS increases the risk of epilepsy. Our data suggest a direct link between severity of MS and epilepsy.

  • 20.
    Burman, Joachim
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Zetterberg, H
    Sahlgrenska Academy, University of Gothenburg.
    Fransson, Moa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Loskog, Angelica SI.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Raininko, Raili
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Fagius, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Assessing tissue damage in multiple sclerosis: a biomarker approach2014Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 130, nr 2, s. 81-89Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES:

    Magnetic resonance imaging (MRI) of the brain and spinal cord is the gold standard for assessing disease activity in multiple sclerosis (MS). MRI is an excellent instrument for determination of accumulated damage to the brain and spinal cord, but tells us little about ongoing tissue damage. In this study, biomarkers of oligodendrocyte, axonal and astrocyte injury were related to MRI and clinical findings and used to assess tissue damage in MS.

    MATERIALS AND METHODS:

    Cerebrospinal fluid from 44 patients with relapsing-remitting MS, 20 with secondary progressive MS and 15 controls were investigated with ELISA to determine levels of myelin basic protein (MBP), neurofilament light (NFL) and glial fibrillary acidic protein (GFAp). Patients underwent MRI of the brain and spinal cord, and gadolinium enhancing lesions, T1 lesions and T2 lesions were counted.

    RESULTS:

    Patients in clinical relapse and patients with nonsymptomatic gadolinium enhancing lesions had high levels of MBP and NFL, indicating ongoing damage to oligodendrocytes and axons. The level of MBP dropped quickly within a week from the onset of a relapse, whereas NFL remained elevated for several weeks and GFAp slowly rose during the course of a relapse. Relapsing-remitting MS patients without gadolinium enhancing lesions had values of MBP, NFL and GFAp similar to controls, while patients with secondary progressive disease had moderately increased values of all biomarkers.

    CONCLUSIONS:

    Analysis of MBP, NFL and GFAp provides direct means to measure tissue damage and is a useful addition to our methods for evaluation of MS.

  • 21.
    Burt, Richard K.
    et al.
    Northwestern Univ, Dept Med, Div Immunotherapy, Feinberg Sch Med, Chicago, IL 60611 USA.
    Balabanov, Roumen
    Northwestern Univ, Feinberg Sch Med, Dept Neurol, Chicago, IL 60611 USA.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Sharrack, Basil
    Sheffield Teaching Hosp NHS Fdn Trust, Dept Neurosci, Sheffield, S Yorkshire, England;Sheffield Teaching Hosp NHS Fdn Trust, Sheffield NIHR Translat Neurosci BBC, Sheffield, S Yorkshire, England;Univ Sheffield, Sheffield, S Yorkshire, England.
    Snowden, John A.
    Univ Sheffield, Sheffield, S Yorkshire, England;Sheffield Teaching Hosp NHS Fdn Trust, Dept Haematol & Oncol, Sheffield, S Yorkshire, England;Sheffield Teaching Hosp NHS Fdn Trust, Dept Metab, Sheffield, S Yorkshire, England.
    Oliveira, Maria Carolina
    Univ Sao Paulo, Ctr Cell Based Therapy, Dept Internal Med, Ribeirao Preto Med Sch, Ribeirao Preto, Brazil.
    Fagius, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Rose, John
    Univ Utah, Dept Neurol, Salt Lake City, UT USA.
    Nelson, Flavia
    Univ Minnesota, Dept Neurol, Div Multiple Sclerosis, Minneapolis, MN 55455 USA.
    Barreira, Amilton Antunes
    Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Neurosci & Behav Sci, Ribeirao Preto, Brazil.
    Carlson, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Han, Xiaoqiang
    Northwestern Univ, Dept Med, Div Immunotherapy, Feinberg Sch Med, Chicago, IL 60611 USA.
    Moraes, Daniela
    Univ Sao Paulo, Ctr Cell Based Therapy, Dept Internal Med, Ribeirao Preto Med Sch, Ribeirao Preto, Brazil.
    Morgan, Amy
    Northwestern Univ, Dept Med, Div Immunotherapy, Feinberg Sch Med, Chicago, IL 60611 USA.
    Quigley, Kathleen
    Northwestern Univ, Dept Med, Div Immunotherapy, Feinberg Sch Med, Chicago, IL 60611 USA.
    Yaung, Kimberly
    Northwestern Univ, Dept Med, Div Immunotherapy, Feinberg Sch Med, Chicago, IL 60611 USA.
    Buckley, Regan
    Northwestern Univ, Dept Med, Div Immunotherapy, Feinberg Sch Med, Chicago, IL 60611 USA.
    Alldredge, Carri
    Northwestern Univ, Dept Med, Div Immunotherapy, Feinberg Sch Med, Chicago, IL 60611 USA.
    Clendenan, Allison
    Northwestern Univ, Dept Med, Div Immunotherapy, Feinberg Sch Med, Chicago, IL 60611 USA.
    Calvario, Michelle A.
    Northwestern Univ, Dept Med, Div Immunotherapy, Feinberg Sch Med, Chicago, IL 60611 USA.
    Henry, Jacquelyn
    Northwestern Univ, Dept Med, Div Immunotherapy, Feinberg Sch Med, Chicago, IL 60611 USA.
    Jovanovic, Borko
    Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
    Helenowski, Irene B.
    Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
    Effect of Nonmyeloablative Hematopoietic Stem Cell Transplantation vs Continued Disease-Modifying Therapy on Disease Progression in Patients With Relapsing-Remitting Multiple Sclerosis: A Randomized Clinical Trial2019Inngår i: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 321, nr 2, s. 165-174Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    IMPORTANCE Hematopoietic stem cell transplantation (HSCT) represents a potentially useful approach to slow or prevent progressive disability in relapsing-remitting multiple sclerosis (MS).

    OBJECTIVE To compare the effect of nonmyeloablative HSCT vs disease-modifying therapy (DMT) on disease progression.

    DESIGN, SETTING, AND PARTICIPANTS Between September 20, 2005, and July 7, 2016, a total of 110 patients with relapsing-remitting MS, at least 2 relapses while receiving DMT in the prior year, and an Expanded Disability Status Scale (EDSS; score range, 0-10 [10 = worst neurologic disability]) score of 2.0 to 6.0 were randomized at 4 US, European, and South American centers. Final follow-up occurred in January 2018 and database lock in February 2018.

    INTERVENTIONS Patients were randomized to receive HSCT along with cyclophosphamide (200mg/kg) and antithymocyte globulin (6mg/kg) (n = 55) or DMT of higher efficacy or a different class than DMT taken during the previous year (n = 55).

    MAIN OUTCOMES AND MEASURES The primary end point was disease progression, defined as an EDSS score increase after at least 1 year of 1.0 point or more (minimal clinically important difference, 0.5) on 2 evaluations 6 months apart, with differences in time to progression estimated as hazard ratios. RESULTS Among 110 randomized patients (73 [66%] women; mean age, 36 [SD, 8.6] years), 103 remained in the trial, with 98 evaluated at 1 year and 23 evaluated yearly for 5 years (median follow-up, 2 years; mean, 2.8 years). Disease progression occurred in 3 patients in the HSCT group and 34 patients in the DMT group. Median time to progression could not be calculated in the HSCT group because of too few events; it was 24 months (interquartile range, 18-48 months) in the DMT group (hazard ratio, 0.07; 95% CI, 0.02-0.24; P < .001). During the first year, mean EDSS scores decreased (improved) from 3.38 to 2.36 in the HSCT group and increased (worsened) from 3.31 to 3.98 in the DMT group (between-group mean difference,-1.7; 95% CI,-2.03 to -1.29; P < .001). There were no deaths and no patients who received HSCT developed nonhematopoietic grade 4 toxicities (such as myocardial infarction, sepsis, or other disabling or potential life-threatening events).

    CONCLUSIONS AND RELEVANCE In this preliminary study of patients with relapsing-remitting MS, nonmyeloablative HSCT, compared with DMT, resulted in prolonged time to disease progression. Further research is needed to replicate these findings and to assess long-term outcomes and safety.

  • 22. Burt, Richard K
    et al.
    Balabanov, Roumen
    Han, Xiaoqiang
    Sharrack, Basil
    Morgan, Amy
    Quigley, Kathleeen
    Yaung, Kim
    Helenowski, Irene B
    Jovanovic, Borko
    Spahovic, Dzemila
    Arnautovic, Indira
    Lee, Daniel C
    Benefield, Brandon C
    Futterer, Stephen
    Oliveira, Maria Carolina
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Association of nonmyeloablative hematopoietic stem cell transplantation with neurological disability in patients with relapsing-remitting multiple sclerosis2015Inngår i: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 313, nr 3, s. 275-284Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    IMPORTANCE: No current therapy for relapsing-remitting multiple sclerosis (MS) results in significant reversal of disability.

    OBJECTIVE: To determine the association of nonmyeloablative hematopoietic stem cell transplantation with neurological disability and other clinical outcomes in patients with MS.

    DESIGN, SETTING, AND PARTICIPANTS: Case series of patients with relapsing-remitting MS (n = 123) or secondary-progressive MS (n = 28) (mean age, 36 years; range, 18-60 years; 85 women) treated at a single US institution between 2003 and 2014 and followed up for 5 years. Final follow-up was completed in June 2014.

    INTERVENTIONS: Treatment with cyclophosphamide and alemtuzumab (22 patients) or cyclophosphamide and thymoglobulin (129 patients) followed by infusion of unmanipulated peripheral blood stem cells.

    MAIN OUTCOMES AND MEASURES: Primary end point was reversal or progression of disability measured by change in the Expanded Disability Status Scale (EDSS) score of 1.0 or greater (score range, 0-10). Secondary outcomes included changes in the Neurologic Rating Scale (NRS) score of 10 or greater (score range, 0-100), Multiple Sclerosis Functional Composite (MSFC) score, quality-of-life Short Form 36 questionnaire scores, and T2 lesion volume on brain magnetic resonance imaging scan.

    RESULTS: Outcome analysis was available for 145 patients with a median follow-up of 2 years and a mean of 2.5 years. Scores from the EDSS improved significantly from a pretransplant median of 4.0 to 3.0 (interquartile range [IQR], 1.5 to 4.0; n = 82) at 2 years and to 2.5 (IQR, 1.9 to 4.5; n = 36) at 4 years (P < .001 at each assessment). There was significant improvement in disability (decrease in EDSS score of ≥1.0) in 41 patients (50%; 95% CI, 39% to 61%) at 2 years and in 23 patients (64%; 95% CI, 46% to 79%) at 4 years. Four-year relapse-free survival was 80% and progression-free survival was 87%. The NRS scores improved significantly from a pretransplant median of 74 to 88.0 (IQR, 77.3 to 93.0; n = 78) at 2 years and to 87.5 (IQR, 75.0 to 93.8; n = 34) at 4 years (P < .001 at each assessment). The median MSFC scores were 0.38 (IQR, -0.01 to 0.64) at 2 years (P < .001) and 0.45 (0.04 to 0.60) at 4 years (P = .02). Total quality-of-life scores improved from a mean of 46 (95% CI, 43 to 49) pretransplant to 64 (95% CI, 61 to 68) at a median follow-up of 2 years posttransplant (n = 132) (P < .001). There was a decrease in T2 lesion volume from a pretransplant median of 8.57 cm3 (IQR, 2.78 to 22.08 cm3) to 5.74 cm3 (IQR, 1.88 to 14.45 cm3) (P < .001) at the last posttransplant assessment (mean follow-up, 27 months; n = 128).

    CONCLUSIONS AND RELEVANCE: Among patients with relapsing-remitting MS, nonmyeloablative hematopoietic stem cell transplantation was associated with improvement in neurological disability and other clinical outcomes. These preliminary findings from this uncontrolled study require confirmation in randomized trials.

  • 23.
    Burt, Richard K.
    et al.
    Northwestern Univ, Div Immunotherapy, Chicago, IL 60611 USA.
    Balabanov, Roumen
    Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA.
    Snowden, John A.
    Sheffield Teaching Hosp, Dept Haematol, Sheffield, S Yorkshire, England.
    Sharrack, Basil
    Sheffield Teaching Hosp, Dept Neurol, Sheffield, S Yorkshire, England.
    Oliveira, Maria Carolina
    Univ Sao Paulo, Sao Paulo, Brazil.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Non-myeloablative hematopoietic stem cell transplantation (HSCT) is superior to disease modifying drug (DMD) treatment in highly active Relapsing Remitting Multiple Sclerosis (RRMS): interim results of the Multiple Sclerosis International Stem cell Transplant (MIST) Randomized Trial2018Inngår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 90Artikkel i tidsskrift (Annet vitenskapelig)
  • 24. Burt, Richard K
    et al.
    Balabanov, Roumen
    Voltarelli, Julio
    Barreira, Amilton
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Autologous hematopoietic stem cell transplantation for multiple sclerosis: if confused or hesitant, remember 'Treat with standard immune suppressive drugs and if no inflammation, no response'2012Inngår i: Multiple Sclerosis Journal, ISSN 1352-4585, Vol. 18, nr 6, s. 772-775Artikkel i tidsskrift (Fagfellevurdert)
  • 25.
    Burt, Richard K.
    et al.
    Northwestern Univ, Div Immunotherapy, Chicago, IL 60611 USA..
    Snowden, John A.
    Sheffield Teaching Hosp NHS Fdn Trust, Dept Haematol, Sheffield, S Yorkshire, England..
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Oliveira, Maria Carolina
    Univ Sao Paulo, Dept Internal Med, Sao Paulo, Brazil..
    Sharrack, Basil
    Sheffield Teaching Hosp NHS Fdn Trust, Dept Neurol, Sheffield, S Yorkshire, England..
    Blogs cannot separate wheat from chaff2017Inngår i: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 358, nr 6363, s. 602-602Artikkel i tidsskrift (Annet vitenskapelig)
  • 26.
    Dagiasi, Loanna
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Dept Clin Neurosci, Gothenburg, Sweden;NAL Hosp Trollhattan, Trollhattan, Sweden.
    Vall, Victor
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Kumlien, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Zelano, Johan
    Univ Gothenburg, Sahlgrenska Acad, Dept Clin Neurosci, Gothenburg, Sweden;Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Treatment of epilepsy in multiple sclerosis2018Inngår i: Seizure, ISSN 1059-1311, E-ISSN 1532-2688, Vol. 58, s. 47-51Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: The prevalence of epilepsy is increased in multiple sclerosis (MS), but information on AED treatment and seizure outcome is scarce. We describe epilepsy characteristics including the use of AEDs and proportion of seizure-free patients at two tertiary hospitals in Sweden. Method: We retrospectively studied electronic medical records of all patients with a diagnosis of MS and seizures at Sahlgrenska university hospital and Uppsala university hospital. Clinical data were reviewed until 2017. Results: We identified a total of 62 MS patients with at least one seizure. Median age at the first seizure (before or after MS) was 41 years (range 0-80). The most common MS disease course at the first seizure was secondary progressive MS, the neurological disability was considerable, and most patients had several MRI lesions at their first seizure. The first EEG demonstrated epileptiform discharges in 38% and unspecific pathology in 40%. Current seizure status could be determined for 37 patients. Out of these, 46% had been seizure free for more than one year at last follow-up. The majority of patients (65%) were on monotherapy at last follow-up. Carbamazepine was the most commonly used first AED, with a retention rate of 52%. No individual AED was associated with a particularly high rate of seizure freedom. The most common reason for discontinuation of the first AED was side-effects. Conclusion: Seizure freedom rates were low, perhaps indicating a need for higher ambitions in management. Side effects of AEDs may be a particular concern when treating epilepsy in patients with MS.

  • 27.
    Das, J.
    et al.
    Sheffield Teaching Hosp NHS Fdn Trust, Acad Dept Neurol, Sheffield, S Yorkshire, England.
    Snowden, J.
    Sheffield Teaching Hosp NHS Fdn Trust, Dept Haematol, Sheffield, S Yorkshire, England.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Freedman, M.
    Univ Ottawa, Dept Med Neurol, Ottawa, ON, Canada;Ottawa Hosp Res Inst, Ottawa, ON, Canada.
    Atkins, H.
    Univ Ottawa, Dept Med Neurol, Ottawa, ON, Canada;Ottawa Hosp Res Inst, Ottawa, ON, Canada.
    Bowman, M.
    Univ Ottawa, Dept Med Neurol, Ottawa, ON, Canada;Ottawa Hosp Res Inst, Ottawa, ON, Canada.
    Burt, R.
    Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA.
    Sarccardi, R.
    Careggi Univ Hosp, Dept Cellular Therapies & Transfus Med, Florence, Italy.
    Innocenti, C.
    Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA.
    Mistry, S.
    Univ Sheffield, Sheffield Med Sch, Sheffield, S Yorkshire, England.
    Bell, S.
    Univ Sheffield, Sheffield Inst Translat Neurosci, Sheffield, S Yorkshire, England.
    Ismail, A.
    Sheffield Teaching Hosp NHS Fdn Trust, Acad Dept Neurol, Sheffield, S Yorkshire, England.
    Jessop, H.
    Sheffield Teaching Hosp NHS Fdn Trust, Dept Haematol, Sheffield, S Yorkshire, England.
    Sharrack, B.
    Sheffield Teaching Hosp NHS Fdn Trust, Acad Dept Neurol, Sheffield, S Yorkshire, England;Univ Sheffield, Sheffield Inst Translat Neurosci, Sheffield, S Yorkshire, England.
    The use of autologous haematopoietic stem cell transplantation as a first line disease modifying therapy in patients with 'aggressive' multiple sclerosis.2018Inngår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, s. 87-88Artikkel i tidsskrift (Annet vitenskapelig)
  • 28.
    Demirbuker, S. Safer
    et al.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Kagström, S.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Fält, A.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Berglund, A.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Hillert, J.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Nilsson, P.
    Lund Univ, Dept Neurol, Lund, Sweden.
    Dahle, C.
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.
    Svenningsson, A.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Lycke, J.
    Univ Gothenburg, Dept Clin Neurosci & Rehabil, Gothenburg, Sweden.
    Landtblom, Anne-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Sundström, P.
    Umea Univ, Dept Clin Neurosci, Umea, Sweden.
    Martin, C.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Gunnarsson, M.
    Orebro Univ, Dept Neurol, Orebro, Sweden.
    Piehl, F.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Olsson, T.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    A Swedish nationwide pharmaco-epidemiological and genetic study of the long-term safety and effectiveness of dimethyl fumarate (IMSE 5)2018Inngår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, s. 701-702Artikkel i tidsskrift (Annet vitenskapelig)
  • 29.
    Demirbuker, S. Safer
    et al.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Kågström, S.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Fält, A.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Hillert, J.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Nilsson, P.
    Lund Univ, Dept Neurol, Lund, Sweden.
    Dahle, C.
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.
    Svenningsson, A.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Lycke, J.
    Univ Gothenburg, Dept Clin Neurosci & Rehabil, Gothenburg, Sweden.
    Landtblom, Anne-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Sundström, P.
    Umea Univ, Dept Clin Neurosci, Umea, Sweden.
    Martin, C.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Gunnarsson, M.
    Orebro Univ, Dept Neurol, Orebro, Sweden.
    Piehl, F.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Olsson, T.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of teriflunomid (IMSE 4)2018Inngår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, s. 922-923Artikkel i tidsskrift (Annet vitenskapelig)
  • 30.
    Fagius, Jan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Normal outcome of pregnancy with ongoing treatment with natalizumab2014Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 129, nr 6, s. e27-e29Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Treatment of multiple sclerosis (MS) with natalizumab during pregnancy is not recommended due to potential risks for the foetus. Despite strong advice accidental pregnancies occur.

    CASE: A 32-year old woman with MS since the age of 26 was treated with natalizumab since January 2008. Treatment was stopped April 2011 due to pregnancy plans, but was restarted following an MS relapse. The patient was thoroughly informed about potential foetal risks, but nevertheless she one year later disclosed that she was pregnant in gestational week 15. Treatment was continued, since the first trimester had passed. The pregnancy course was normal and a healthy daughter was born at full gestational term.

    CONCLUSIONS: This is the second known case where natalizumab treatment continued throughout the whole gestational period.

  • 31.
    Fagius, Jan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Feresiadou, Amalia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Severe relapses and rebound activity after natalizumab discontinuation in MS patients with more than five years of treatment with stable disease course2015Inngår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, s. 297-297Artikkel i tidsskrift (Annet vitenskapelig)
  • 32.
    Fagius, Jan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Feresiadou, Amalia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Discontinuation of disease modifying treatments in middle aged multiple sclerosis patients: First line drugs vs natalizumab2017Inngår i: Multiple Sclerosis and Related Disorders, ISSN 2211-0348, E-ISSN 2211-0356, Vol. 12, s. 82-87, artikkel-id S2211-0348(17)30010-XArtikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Several disease-modifying drugs (DMD) are available for the treatment of MS, and most patients with relapsing-remitting disease are currently treated. Data on when and how DMD treatment can be safely discontinued are scarce.

    METHODS: Fifteen MS patients, treated with natalizumab for >5 years without clinical and radiological signs of inflammatory disease activity, suspended treatment and were monitored with MRI examinations and clinical follow-up to determine recurrence of disease activity. This group was compared with a retrospectively analysed cohort comprising 55 MS patients treated with first-line DMDs discontinuing therapy in the time period of 1998-2015 after an analogous stable course.

    RESULTS: Natalizumab discontinuers were followed for on average 19 months, and follow-up data for 56 months were available for first-line DMD quitters. Two-thirds of natalizumab treated patients experienced recurrent inflammatory disease activity, and one third had recurrence of rebound character. In contrast, 35% of first-line DMD quitters had mild recurrent disease activity, and no one exhibited rebound.

    CONCLUSIONS: Withdrawal of a first-line DMD after prolonged treatment in middle-aged MS patients with stable disease appears to be relatively safe, while natalizumab withdrawal in a similar group of patients cannot be safely done without starting alternative therapy.

  • 33.
    Feresiadou, Amalia
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Landtblom: Neurologi.
    Nilsson, Kenneth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Ingelsson, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Press, Rayomand
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden..
    Kmezic, Ivan
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden..
    Nygren, Ingela
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Svenningsson, Anders
    Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden..
    Niemelä, Valter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Gordh, Torsten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Cunningham, Janet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Kultima, Kim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Measurement of sCD27 in the cerebrospinal fluid identifies patients with neuroinflammatory disease2019Inngår i: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 332, s. 31-36Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Laboratory tests to assist in the diagnosis and monitoring of neuroinflammatory diseases are scarce. The soluble form of the CD27 molecule (sCD27) is shed in high concentrations by activated T cells and can be detected in the cerebrospinal fluid. The aim of this study was to investigate whether CSF quantitation of sCD27 could discriminate between inflammatory and non-inflammatory neurological diseases.

    METHODS: The concentration of sCD27 was measured using a commercially available ELISA in 803 well-defined subjects from a study cohort comprised of 338 patients with neuroinflammatory disease, 338 with non-inflammatory neurological disease and 127 controls without neurological disease.

    RESULTS: The median value of cerebrospinal fluid sCD27 was 64 pg/mL (IQR 0-200) in controls, 58 pg/mL (IQR 0-130) in patients with non-inflammatory disease and 740 pg/mL (IQR 230-1800) in patients with inflammatory disease. The likelihood ratio of having an inflammatory disease was 10 (sensitivity 74% and specificity 93%) if the sCD27 concentration was >250 pg/mL. In patients with a known inflammatory condition, the likelihood ratio of having an infection was 10 (sensitivity 40% and specificity 96%) if the sCD27 concentration was >2500 pg/mL.

    CONCLUSIONS: The likelihood of having an inflammatory neurological condition is increased with elevated concentrations of sCD27 in cerebrospinal fluid. Rapid tests of sCD27 should be developed to assist clinicians in diagnosis of neuroinflammatory disease.

  • 34.
    Forsberg, L.
    et al.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Johansson, S.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Frisell, T.
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Hillert, J.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Nilsson, P.
    Lund Univ, Dept Clin Sci, Neurol, Lund, Sweden..
    Dahle, C.
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Sveningsson, A.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Lycke, J.
    Univ Gothenburg, Dept Clin Neurosci & Rehabil, Gothenburg, Sweden..
    Landtblom, A-M
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Walentin, F.
    Orebro Univ Hosp, Orebro, Sweden..
    Martin, C.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Piehl, F.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Olsson, T.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Real world experience of fingolimod after switching multiple sclerosis (MS) therapy; focus on natalizumab naive and experienced persons with MS, respectively2016Inngår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 22, nr Suppl. 3, s. 647-648Artikkel i tidsskrift (Fagfellevurdert)
  • 35.
    Forsberg, L.
    et al.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Johansson, S.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Hillert, J.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Nilsson, P.
    Lund Univ, Neurol, Dept Clin Sci, Lund, Sweden..
    Dahle, C.
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Sveningsson, A.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Lycke, J.
    Univ Gothenburg, Dept Clin Neurosci & Rehabil, Gothenburg, Sweden..
    Landtblom, A-M
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala Univ, Dept Neurosci, Uppsala, Sweden..
    Walentin, F.
    Orebro Univ Hosp, Orebro, Sweden..
    Martin, C.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Piehl, F.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Olsson, T.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    A Swedish nationwide pharmaco-epidemiological and genetic study of the long-term safety and effectiveness of dimethyl fumarate (IMSE 5)2016Inngår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 22, nr Suppl. 3, s. 338-339Artikkel i tidsskrift (Fagfellevurdert)
  • 36.
    Forsberg, L.
    et al.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Johansson, S.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Nordin, N.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Hillert, J.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Svenningsson, A.
    Umea Univ, Pharmacol & Clin Neurosci, Umea, Sweden..
    Lycke, J.
    Univ Gothenburg, Dept Clin Neurosci & Rehabil, Gothenburg, Sweden..
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Landtblom, Anne-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Walentin, F.
    Orebro Univ Hosp, Orebro, Sweden..
    Martin, C.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Nilsson, P.
    Lund Univ, Dept Neurol, Lund, Sweden..
    Dahle, C.
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Piehl, F.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Olsson, T.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    A Swedish nationwide pharmaco-epidemiological and genetic study (IMSE) of the long-term safety and efficacy of dimethyl fumarate2015Inngår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, s. 286-287Artikkel i tidsskrift (Annet vitenskapelig)
  • 37.
    Forsberg, L.
    et al.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Kagstrom, S.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Leandersson, A.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Berglund, A.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Biogen, Med Dept, Upplandsvasby, Sweden..
    Hillert, J.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Nilsson, P.
    Lund Univ, Dept Neurol, Lund, Sweden..
    Dahle, C.
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Sveningsson, A.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Lycke, J.
    Univ Gothenburg, Dept Clin Neurosci & Rehabil, Gothenburg, Sweden..
    Landtblom, Anne-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Walentin, F.
    Orebro Univ Hosp, Orebro, Sweden..
    Martin, C.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Piehl, F.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Olsson, T.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of dimethyl fumarate (IMSE 5)2017Inngår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 23, s. 884-885Artikkel i tidsskrift (Annet vitenskapelig)
  • 38.
    Forsberg, L.
    et al.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Leandersson, A.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Kagstrom, S.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Hillert, J.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Nilsson, P.
    Lund Univ, Dept Neurol, Lund, Sweden..
    Dahle, C.
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Sveningsson, A.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Lycke, J.
    Univ Gothenburg, Dept Clin Neurosci & Rehabil, Gothenburg, Sweden..
    Landtblom, Anne-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Walentin, F.
    Orebro Univ Hosp, Orebro, Sweden..
    Martin, C.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Piehl, F.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Olsson, T.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of teriflunomid (IMSE 4)2017Inngår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 23, s. 635-636Artikkel i tidsskrift (Annet vitenskapelig)
  • 39.
    Fransson, Moa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för klinisk immunologi.
    Piras, E
    Wang, H
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Duprez, I
    Harris, R
    LeBlanc, K
    Brittebo, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Loskog, Angelica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Human Mesenchymal stromal cells expressing a CNS-targeting receptor can be administrated intra nasally and cure expersimental autoimmune enchphlomyelitisManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Mesenchymal stromal cells (MSCs) are a heterogeneous population of stromal cells residing in most connective tissues and have the capacity to suppress effector cells of the immune system. In experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, systemic treatments with both murine and human MSCs have proven beneficial because of their capacity to suppress overt immune reactions. However, systemic administration of such cells may cause problems with infectious disease and low numbers of cells that reach the inflamed tissue. We hypothesized that MSCs can be accumulated and retained in the CNS using gene transfer of a CNS-targeting device and intranasal cell delivery. In the current investigation, MSCs were engineered to express a myelin oligodendrocyte glycoprotein (MOG)-specific receptor using lentiviral vectors. Genetically engineered MSCs retained their suppressive capacity in vitro and successfully targeted the brain upon both intraperitoneal and intranasal delivery. Engineered MSCs cured mice from disease symptoms and these mice were resistant to further EAE challenge. Encephalitic T cells isolated from cured mice displayed an anergic profile while peripheral T cells were still responsive to stimuli. Further, MSC treatment reduced the level of inflammatory cytokines in the brain and implyed reduced damage to axons. In conclusion, MSCs can be genetically engineered to target CNS and efficiently suppress encephalomyelitis in an active EAE model upon intranasal delivery.

  • 40.
    Fransson, Moa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för klinisk immunologi.
    Piras, E
    Wang, H
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Harris, R
    Brittebo, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Loskog, Angelica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Engineered T regulatory cells target CNS and suppress active EAE upon intra nasal deliveryManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system (CNS). In the murine experimental autoimmune encephalomyelitis (EAE) model of MS, T regulatory (Treg) cell therapy has proven beneficial. However, systemic administration of such cells may immunologically compromise the recipient and promote infections due to general immunosuppression. We hypothesized that Tregs can be equipped with a CNS-targeting receptor and be delivered intra-nasally to avoid systemic exposure. In the current investigation, CD4+ T cells were modified with a lentiviral vector system to express a myelin oligodendrocyte (MOG)-targeting receptor in trans with the FoxP3 gene that drives Treg differentiation. The genetically engineered Tregs demonstrated suppressive capacity in vitro and were then tested in the EAE model. Engineered Tregs localized to the brain and suppressed ongoing encephalomyelitis in vivo. Cured mice were rechallenged with an EAE-inducing inoculum but remained healthy. Cytokine profile of the brain reveled lower levels of effector cytokines in TregCAR treated mice and acordingly, reduced axonal damage was seen in these mice. In conclusion, CNS-specific Tregs were able to localize to the CNS and efficiently cure mice with ongoing EAE.

  • 41.
    Fransson, Moa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Piras, Elena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Nilsson, Berith
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Essand, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lu, Binfeng
    Harris, Robert A
    Magnusson, Peetra U
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Brittebo, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Loskog, Angelica Si
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    CAR/FoxP3-engineered T regulatory cells target the CNS and suppress EAE upon intranasal delivery2012Inngår i: Journal of Neuroinflammation, ISSN 1742-2094, E-ISSN 1742-2094, Vol. 9, s. 112-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS). In the murine experimental autoimmune encephalomyelitis (EAE) model of MS, T regulatory (Treg) cell therapy has proved to be beneficial, but generation of stable CNS-targeting Tregs needs further development. Here, we propose gene engineering to achieve CNS-targeting Tregs from naive CD4 cells and demonstrate their efficacy in the EAE model.

    METHODS

    CD4+T cells were modified utilizing a lentiviral vector system to express a chimeric antigen receptor (CAR) targeting myelin oligodendrocyte glycoprotein (MOG) in trans with the murine FoxP3 gene that drives Treg differentiation. The cells were evaluated in vitro for suppressive capacity and in C57BL/6 mice to treat EAE. Cells were administered by intranasal (i.n.) cell delivery.

    RESULTS

    The engineered Tregs demonstrated suppressive capacity in vitro and could efficiently access various regions in the brain via i.n cell delivery. Clinical score 3 EAE mice were treated and the engineered Tregs suppressed ongoing encephalomyelitis as demonstrated by reduced disease symptoms as well as decreased IL-12 and IFNgamma mRNAs in brain tissue. Immunohistochemical markers for myelination (MBP) and reactive astrogliosis (GFAP) confirmed recovery in mice treated with engineered Tregs compared to controls. Symptomfree mice were echallenged with a second EAE-inducing inoculum but remained healthy, demonstrating the sustained effect of engineered Tregs.

    CONCLUSION

    CNS-targeting Tregs delivered i.n. localized to the CNS and efficiently suppressed ongoing inflammation leading to diminished disease symptoms.

  • 42.
    Fransson, Moa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Piras, Elena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Wang, Hao
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Duprez, Ida
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Harris, Robert A
    Leblanc, Katarina
    Magnusson, Peetra U
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Brittebo, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Loskog, Angelica S I
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Intranasal Delivery of CNS-Retargeted Human Mesenchymal Stromal Cells Prolongs Treatment Efficacy of Experimental Autoimmune Encephalomyelitis2014Inngår i: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 142, nr 3, s. 431-441Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Treatment with mesenchymal stromal cells (MSC) is currently of interest for a number of diseases including multiple sclerosis (MS). MSCs is well known to target inflamed tissues however, in a therapeutic scenery, systemic administration will lead to few cells reaching the brain. We hypothesized that MSCs may target the brain upon intranasal (i.n) administration and persist in CNS tissue if expressing a CNS-targeting receptor. To demonstrate proof of concept, MSCs were genetically engineered to express a myelin oligodendrocyte glycoprotein (MOG)-specific receptor. Engineered MSCs retained their immunosuppressive capacity, infiltrated into the brain upon i.n. cell administration, and were able to significantly reduce disease symptoms of experimental autoimmune encephalomyelitis (EAE). The mice treated with CNS-targeting MSCs were resistant to further EAE induction whereas non-targeted MSC did not give such persistent effects. Histological analysis revealed increased brain restoration in engineered MSC-treated mice. In conclusion, MSCs can be genetically engineered to target the brain and prolong therapeutic efficacy in an EAE model.

  • 43.
    Fält, A.
    et al.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Kagstrom, S.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Demirbuker, S. Safer
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Hillert, J.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Nilsson, P.
    Lund Univ, Dept Neurol, Lund, Sweden.
    Dahle, C.
    Linkoping Univ, Dept Clin & Expt Med, Linkopinig, Sweden.
    Svenningsson, A.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Lycke, J.
    Univ Gothenburg, Dept Clin Neurosci & Rehabil, Gothenburg, Sweden.
    Landtblom, Anne-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Martin, C.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Sundström, P.
    Umea Univ, Dept Clin Neurosci, Umea, Sweden.
    Gunnarsson, M.
    Orebro Univ, Dept Neurol, Orebro, Sweden.
    Piehl, F.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Olsson, T.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of fingolimod (IMSE 2)2018Inngår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, s. 696-697Artikkel i tidsskrift (Annet vitenskapelig)
  • 44.
    Fält, A.
    et al.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Kågström, S.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Demirbuker, S. Safer
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Hillert, J.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Nilsson, P.
    Lund Univ, Dept Neurol, Lund, Sweden.
    Dahle, C.
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.
    Svenningsson, A.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Lycke, J.
    Univ Gothenburg, Dept Clin Neurosci & Rehabil, Gothenburg, Sweden.
    Landtblom, Anne-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Martin, C.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Sundström, P.
    Umea Univ, Dept Clin Neurosci, Umea, Sweden.
    Gunnarsson, M.
    Orebro Univ, Dept Neurol, Orebro, Sweden.
    Piehl, F.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Olsson, T.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of alemtuzumab (IMSE 3)2018Inngår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, s. 706-707Artikkel i tidsskrift (Annet vitenskapelig)
  • 45. Greco, Raffaella
    et al.
    Bondanza, Attilio
    Oliveira, Maria Carolina
    Badoglio, Manuela
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Piehl, Fredrik
    Hägglund, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Krasulova, Eva
    Simões, Belinda Pinto
    Carlson, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Pohlreich, David
    Labopin, Myriam
    Saccardi, Riccardo
    Comi, Giancarlo
    Mancardi, Gian Luigi
    Bacigalupo, Andrea
    Ciceri, Fabio
    Farge, Dominique
    Autologous hematopoietic stem cell transplantation in neuromyelitis optica: A registry study of the EBMT Autoimmune Diseases Working Party2015Inngår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, nr 2, s. 189-197Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    Neuromyelitis optica (NMO) is an inflammatory autoimmune disorder of the central nervous system, hallmarked by pathogenic anti-aquaporin 4 antibodies. NMO prognosis is worse compared with multiple sclerosis.

    OBJECTIVE:

    The European Group for Blood and Marrow Transplantation (EBMT) Autoimmune Diseases Working Party (ADWP) conducted a retrospective survey to analyze disease outcome following autologous stem cell transplantation (ASCT).

    METHODS:

    This retrospective multicenter study assessed the efficacy and safety of ASCT in 16 patients suffering from refractory NMO reported to the EBMT registry between 2001 and 2011.

    RESULTS:

    Fifteen patients were successfully mobilized with cyclophosphamide (Cy) and G-CSF, one with G-CSF alone. All patients received an unmanipulated autologous peripheral blood stem cell graft, after conditioning with BEAM plus anti-thymocyte globulin (ATG, n = 9 patients), thiotepa-Cy (n = 3) or Cy (200 mg/kg) plus ATG (n = 4). After a median follow-up of 47 months, three of 16 cases were progression and treatment free, while in the remaining 13 patients further treatments were administered for disability progression or relapse after ASCT. Altogether, relapse-free survival at three and five years was 31% and 10%, respectively, while progression-free survival remained 48% at three and five years.

    CONCLUSIONS:

    In these NMO patients, highly resistant to conventional treatment, ASCT allows for temporary control of the disease, despite a tendency to progress or relapse in the long term.

  • 46.
    Herman, Stephanie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Emami Khoonsari, Payam
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Tolf, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Steinmetz, Julia
    Zetterberg, Henrik
    Åkerfeldt, Torbjörn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Jakobsson, Per-Johan
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Spjuth, Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Kultima, Kim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Integration of magnetic resonance imaging and protein and metabolite CSF measurements to enable early diagnosis of secondary progressive multiple sclerosis.2018Inngår i: Theranostics, ISSN 1838-7640, E-ISSN 1838-7640, Vol. 8, nr 16, s. 4477-4490Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Molecular networks in neurological diseases are complex. Despite this fact, contemporary biomarkers are in most cases interpreted in isolation, leading to a significant loss of information and power. We present an analytical approach to scrutinize and combine information from biomarkers originating from multiple sources with the aim of discovering a condensed set of biomarkers that in combination could distinguish the progressive degenerative phenotype of multiple sclerosis (SPMS) from the relapsing-remitting phenotype (RRMS).

    Methods: Clinical and magnetic resonance imaging (MRI) data were integrated with data from protein and metabolite measurements of cerebrospinal fluid, and a method was developed to sift through all the variables to establish a small set of highly informative measurements. This prospective study included 16 SPMS patients, 30 RRMS patients and 10 controls. Protein concentrations were quantitated with multiplexed fluorescent bead-based immunoassays and ELISA. The metabolome was recorded using liquid chromatography-mass spectrometry. Clinical follow-up data of the SPMS patients were used to assess disease progression and development of disability.

    Results: Eleven variables were in combination able to distinguish SPMS from RRMS patients with high confidence superior to any single measurement. The identified variables consisted of three MRI variables: the size of the spinal cord and the third ventricle and the total number of T1 hypointense lesions; six proteins: galectin-9, monocyte chemoattractant protein-1 (MCP-1), transforming growth factor alpha (TGF-α), tumor necrosis factor alpha (TNF-α), soluble CD40L (sCD40L) and platelet-derived growth factor AA (PDGF-AA); and two metabolites: 20β-dihydrocortisol (20β-DHF) and indolepyruvate. The proteins myelin basic protein (MBP) and macrophage-derived chemokine (MDC), as well as the metabolites 20β-DHF and 5,6-dihydroxyprostaglandin F1a (5,6-DH-PGF1), were identified as potential biomarkers of disability progression.

    Conclusion: Our study demonstrates, in a limited but well-defined and data-rich cohort, the importance and value of combining multiple biomarkers to aid diagnostics and track disease progression.

  • 47.
    Herman, Stephanie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Niemelä, Valter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Emami Khoonsari, Payam
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Sundblom, Jimmy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Landtblom, Anne-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Spjuth, Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Nyholm, Dag
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Kultima, Kim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Alterations in the tyrosine and phenylalanine pathways revealed by biochemical profiling in cerebrospinal fluid of Huntington's disease subjects2019Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, artikkel-id 4129Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Huntington's disease (HD) is a severe neurological disease leading to psychiatric symptoms, motor impairment and cognitive decline. The disease is caused by a CAG expansion in the huntingtin (HTT) gene, but how this translates into the clinical phenotype of HD remains elusive. Using liquid chromatography mass spectrometry, we analyzed the metabolome of cerebrospinal fluid (CSF) from premanifest and manifest HD subjects as well as control subjects. Inter-group differences revealed that the tyrosine metabolism, including tyrosine, thyroxine, L-DOPA and dopamine, was significantly altered in manifest compared with premanifest HD. These metabolites demonstrated moderate to strong associations to measures of disease severity and symptoms. Thyroxine and dopamine also correlated with the five year risk of onset in premanifest HD subjects. The phenylalanine and the purine metabolisms were also significantly altered, but associated less to disease severity. Decreased levels of lumichrome were commonly found in mutated HTT carriers and the levels correlated with the five year risk of disease onset in premanifest carriers. These biochemical findings demonstrates that the CSF metabolome can be used to characterize molecular pathogenesis occurring in HD, which may be essential for future development of novel HD therapies.

  • 48.
    Herman, Stephanie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Åkerfeldt, Torbjörn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Spjuth, Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Kultima, Kim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Biochemical Differences in Cerebrospinal Fluid between Secondary Progressive and Relapsing-Remitting Multiple Sclerosis2019Inngår i: Cells, ISSN 2073-4409, Vol. 8, nr 2, artikkel-id 84Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To better understand the pathophysiological differences between secondary progressive multiple sclerosis (SPMS) and relapsing-remitting multiple sclerosis (RRMS), and to identify potential biomarkers of disease progression, we applied high-resolution mass spectrometry (HRMS) to investigate the metabolome of cerebrospinal fluid (CSF). The biochemical differences were determined using partial least squares discriminant analysis (PLS-DA) and connected to biochemical pathways as well as associated to clinical and radiological measures. Tryptophan metabolism was significantly altered, with perturbed levels of kynurenate, 5-hydroxytryptophan, 5-hydroxyindoleacetate, and N-acetylserotonin in SPMS patients compared with RRMS and controls. SPMS patients had altered kynurenine compared with RRMS patients, and altered indole-3-acetate compared with controls. Regarding the pyrimidine metabolism, SPMS patients had altered levels of uridine and deoxyuridine compared with RRMS and controls, and altered thymine and glutamine compared with RRMS patients. Metabolites from the pyrimidine metabolism were significantly associated with disability, disease activity and brain atrophy, making them of particular interest for understanding the disease mechanisms and as markers of disease progression. Overall, these findings are of importance for the characterization of the molecular pathogenesis of SPMS and support the hypothesis that the CSF metabolome may be used to explore changes that occur in the transition between the RRMS and SPMS pathologies.

  • 49.
    Innocenti, C.
    et al.
    Careggi Univ Hosp, Hematol, Florence, Italy; Northwestern Hosp, Dept Immunotherapy & Autoimmune Dis, Chicago, IL USA.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Burns, C.
    Northwestern Univ, Dept Immunotherapy & Autoimmune Dis, Chicago, IL USA.
    Burt, R.
    Northwestern Hosp, Dept Immunotherapy & Autoimmune Dis, Chicago, IL USA.
    Inflammatory immune response after autologous transplantation in neurologic diseases2017Inngår i: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 52, nr Supplement: 1, s. S420-S420Artikkel i tidsskrift (Annet vitenskapelig)
  • 50.
    Johansson, S.
    et al.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Forsberg, L.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Hillert, J.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Nilsson, P.
    Lund Univ, Dept Neurol, Lund, Sweden..
    Dahle, C.
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Svenningsson, A.
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Danderyd, Sweden..
    Lycke, J.
    Univ Gothenburg, Dept Clin Neurosci & Rehabil, Gothenburg, Sweden..
    Landtblom, A-M
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi. Uppsala Univ, Dept Neurosci, Uppsala, Sweden..
    Walentin, F.
    Orebro Univ Hosp, Orebro, Sweden..
    Martin, C.
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Danderyd, Sweden..
    Piehl, F.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Olsson, T.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    A Swedish nationwide pharmaco-epidemiological and genetic study of the long-term safety and effectiveness of natalizumab (IMSE 1)2016Inngår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 22, nr suppl. 3, s. 336-337Artikkel i tidsskrift (Fagfellevurdert)
12 1 - 50 of 70
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