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9. Altered cortical synaptic lipid signaling leads to intermediate phenotypes of mental disorders

Author

Tüscher, Oliver, primary, Muthuraman, Muthuraman, additional, Horstmann, Johann-Philipp, additional, Horta, Guilherme, additional, Radyushkin, Konstantin, additional, Baumgart, Jan, additional, Sigurdsson, Torfi, additional, Endle, Heiko, additional, Ji, Haichao, additional, Kuhnhäuser, Prisca, additional, Götz, Jan, additional, Kepser, Lara-Jane, additional, Lotze, Martin, additional, Grabe, Hans J., additional, Völzke, Henry, additional, Leehr, Elisabeth J., additional, Meinert, Susanne, additional, Opel, Nils, additional, Richers, Sebastian, additional, Stroh, Albrecht, additional, Daun, Silvia, additional, Tittgemeyer, Marc, additional, Uphaus, Timo, additional, Steffen, Falk, additional, Zipp, Frauke, additional, Groß, Joachim, additional, Groppa, Sergiu, additional, Dannlowski, Udo, additional, Nitsch, Robert, additional, and Vogt, Johannes, additional

Published
2024
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11. Clinical and Diagnostic Features of Post-Acute COVID-19 Vaccination Syndrome (PACVS).

Author

Mundorf, Anna Katharina, Semmler, Amelie, Heidecke, Harald, Schott, Matthias, Steffen, Falk, Bittner, Stefan, Lackner, Karl J., Schulze-Bosse, Karin, Pawlitzki, Marc, Meuth, Sven Guenther, Klawonn, Frank, Ruhrländer, Jana, and Boege, Fritz

Subjects
CHRONIC fatigue syndrome, RECEPTOR antibodies, ADRENERGIC receptors, BIOMARKERS, ANGIOTENSIN II
Abstract

Post-acute COVID-19 vaccination syndrome (PACVS) is a chronic disease triggered by SARS-CoV-2 vaccination (estimated prevalence 0.02%). PACVS is discriminated from the normal post-vaccination state by altered receptor antibodies, most notably angiotensin II type 1 and alpha-2B adrenergic receptor antibodies. Here, we investigate the clinical phenotype using a study registry encompassing 191 PACVS-affected persons (159 females/32 males; median ages: 39/42 years). Unbiased clustering (modified Jaccard index) of reported symptoms revealed a prevalent cross-cohort symptomatology of malaise and chronic fatigue (>80% of cases). Overlapping clusters of (i) peripheral nerve dysfunction, dysesthesia, motor weakness, pain, and vasomotor dysfunction; (ii) cardiovascular impairment; and (iii) cognitive impairment, headache, and visual and acoustic dysfunctions were also frequently represented. Notable abnormalities of standard serum markers encompassing increased interleukins 6 and 8 (>80%), low free tri-iodine thyroxine (>80%), IgG subclass imbalances (>50%), impaired iron storage (>50%), and increased soluble neurofilament light chains (>30%) were not associated with specific symptoms. Based on these data, 131/191 participants fit myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and simultaneously also several other established dysautonomia syndromes. Furthermore, 31/191 participants fit none of these syndromes. In conclusion, PACVS could either be an outlier of ME/CFS or a dysautonomia syndrome sui generis. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Relevance of dedicated multiple sclerosis serum biomarkers in predicting contrast enhancement with gadolinium ‐ Results from the REDUCE‐GAD trial

Author

Schaefer, Jan Hendrik, primary, Schaller‐Paule, Martin A., additional, Wenger, Katharina, additional, Mayer, Christoph, additional, Mann, Ulrike, additional, Bickert, Alexander, additional, Steffen, Falk, additional, Bittner, Stefan, additional, Yalachkov, Yavor, additional, and Foerch, Christian, additional

Published
2023
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19. IL-17+ CD8+ T cell suppression by dimethyl fumarate associates with clinical response in multiple sclerosis

Author

Lückel, Christina, Picard, Felix, Raifer, Hartmann, Campos Carrascosa, Lucia, Guralnik, Anna, Zhang, Yajuan, Klein, Matthias, Bittner, Stefan, Steffen, Falk, Moos, Sonja, Marini, Federico, Gloury, Renee, Kurschus, Florian C., Chao, Ying-Yin, Bertrams, Wilhelm, Sexl, Veronika, Schmeck, Bernd, Bonetti, Lynn, Grusdat, Melanie, Lohoff, Michael, Zielinski, Christina E., Zipp, Frauke, Kallies, Axel, Brenner, Dirk, Berger, Michael, Bopp, Tobias, Tackenberg, Björn, and Huber, Magdalena

Published
2019
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25. Absolute serum neurofilament light chain levels and its early kinetics predict brain injury after out-of-hospital cardiac arrest

Author

Simon Braumann, Stephan Baldus, Steffen Falk, Clemens Warnke, Christoph Adler, Gereon R. Fink, Stefan Bittner, Oezguer A. Onur, and Hannes Gramespacher

Subjects
medicine.medical_specialty, Neurology, Neurofilament light, Intermediate Filaments, Out of hospital cardiac arrest, 03 medical and health sciences, 0302 clinical medicine, Neurofilament Proteins, Internal medicine, medicine, Humans, ddc:610, Retrospective Studies, Neuroradiology, business.industry, Cerebral hypoxia, 030208 emergency & critical care medicine, Retrospective cohort study, Prognosis, Serum samples, Clinical routine, medicine.disease, Kinetics, Brain Injuries, Cardiology, Neurology (clinical), business, Biomarkers, Out-of-Hospital Cardiac Arrest, 030217 neurology & neurosurgery
Abstract

Objectives To test if the early kinetics of neurofilament light (NFL) in blood adds to the absolute values of NFL in the prediction of outcome, and to evaluate if NFL can discriminate individuals with severe hypoxic–ischemic brain injury (sHIBI) from those with other causes of poor outcome after out-of-hospital cardiac arrest (OHCA). Design and setting Monocentric retrospective study involving individuals following non-traumatic OHCA between April 2014 and April 2016. NFL concentrations were determined on a SiMoA HD-1 device using NF-Light Advantage Kits. Participants Of 73 patients screened, 53 had serum samples available for NFL measurement at three timepoints (after 3, 24, and 48 h of admission). Of these 53 individuals, 43.4% had poor neurologic outcome at discharge as assessed by Glasgow–Pittsburgh cerebral performance categories, and, according to a current prognostication algorithm, poor outcome due to sHIBI in 20.7%. Main outcome measure Blood NFL and its early kinetics for prognostication of outcome and prediction of sHIBI after OHCA. Results An absolute NFL > 508.6 pg/ml 48 h after admission, or a change in NFL > 494 pg/ml compared with an early baseline value predicted outcome, and discriminated severe sHIBI from other causes of unfavorable outcome after OHCA with high sensitivity (100%, 95%CI 70.0–100%) and specificity (91.7%, 95%CI 62.5–100%). Conclusions Not only absolute values of NFL, but also early changes in NFL predict the outcome following OHCA, and may differentiate sHIBI from other causes of poor outcome after OHCA with high sensitivity and specificity. Our study adds to published data, overall corroborating that NFL measured in blood should be implemented in prognostication algorithms used in clinical routine.

Published
2021

27. Detecting ongoing disease activity in mildly affected multiple sclerosis patients under first-line therapies

Author

Masanneck, Lars, primary, Rolfes, Leoni, additional, Regner-Nelke, Liesa, additional, Willison, Alice, additional, Räuber, Saskia, additional, Steffen, Falk, additional, Bittner, Stefan, additional, Zipp, Frauke, additional, Albrecht, Philipp, additional, Ruck, Tobias, additional, Hartung, Hans-Peter, additional, Meuth, Sven G., additional, and Pawlitzki, Marc, additional

Published
2022
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28. Brain-derived neurotrophic factor and neurofilament light chain in cerebrospinal fluid are inversely correlated with cognition in Multiple Sclerosis at the time of diagnosis

Author

Yalachkov, Yavor, primary, Anschütz, Victoria, additional, Jakob, Jasmin, additional, Schaller-Paule, Martin A., additional, Schäfer, Jan Hendrik, additional, Reiländer, Annemarie, additional, Friedauer, Lucie, additional, Behrens, Marion, additional, Steffen, Falk, additional, Bittner, Stefan, additional, and Foerch, Christian, additional

Published
2022
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29. Inhibition of the enzyme autotaxin reduces cortical excitability and ameliorates the outcome in stroke

Author

Bitar, Lynn, Uphaus, Timo, Thalman, Carine, Muthuraman, Muthuraman, Gyr, Luzia, Ji, Haichao, Domingues, Micaela, Endle, Heiko, Groppa, Sergiu, Steffen, Falk, Koirala, Nabin, Fan, Wei, Ibanez, Laura, Heitsch, Laura, Cruchaga, Carlos, Lee, Jin-Moo, Kloss, Florian, Bittner, Stefan, Nitsch, Robert, Zipp, Frauke, Vogt, Johannes, Bitar, Lynn, Uphaus, Timo, Thalman, Carine, Muthuraman, Muthuraman, Gyr, Luzia, Ji, Haichao, Domingues, Micaela, Endle, Heiko, Groppa, Sergiu, Steffen, Falk, Koirala, Nabin, Fan, Wei, Ibanez, Laura, Heitsch, Laura, Cruchaga, Carlos, Lee, Jin-Moo, Kloss, Florian, Bittner, Stefan, Nitsch, Robert, Zipp, Frauke, and Vogt, Johannes

Abstract

Stroke penumbra injury caused by excess glutamate is an important factor in determining stroke outcome; however, several therapeutic approaches aiming to rescue the penumbra have failed, likely due to unspecific targeting and persistent excitotoxicity, which continued far beyond the primary stroke event. Synaptic lipid signaling can modulate glutamatergic transmission via presynaptic lysophosphatidic acid (LPA) 2 receptors modulated by the LPA- synthesizing molecule autotaxin (ATX) present in astrocytic perisynaptic processes. Here, we detected long-lasting increases in brain ATX concentrations after experimental stroke. In humans, cerebrospinal fluid ATX concentration was increased up to 14 days after stroke. Using astrocyte-specific deletion and pharmacological inhibition of ATX at different time points after experimental stroke, we showed that inhibition of LPA-related cortical excitability improved stroke outcome. In transgenic mice and in individuals expressing a single-nucleotide polymorphism that increased LPA-related glutamatergic transmission, we found dysregulated synaptic LPA signaling and subsequent negative stroke outcome. Moreover, ATX inhibition in the animal model ameliorated stroke outcome, suggesting that this approach might have translational potential for improving the outcome after stroke.

Published
2022

30. Alemtuzumab-induced immune phenotype and repertoire changes: implications for secondary autoimmunity

Author

Ruck, Tobias, primary, Barman, Sumanta, additional, Schulte-Mecklenbeck, Andreas, additional, Pfeuffer, Steffen, additional, Steffen, Falk, additional, Nelke, Christopher, additional, Schroeter, Christina B., additional, Willison, Alice, additional, Heming, Michael, additional, Müntefering, Thomas, additional, Melzer, Nico, additional, Krämer, Julia, additional, Lindner, Maren, additional, Riepenhausen, Marianne, additional, Gross, Catharina C., additional, Klotz, Luisa, additional, Bittner, Stefan, additional, Muraro, Paolo A., additional, Schneider-Hohendorf, Tilman, additional, Schwab, Nicholas, additional, Meyer zu Hörste, Gerd, additional, Goebels, Norbert, additional, Meuth, Sven G., additional, and Wiendl, Heinz, additional

Published
2022
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31. Inhibition of the enzyme autotaxin reduces cortical excitability and ameliorates the outcome in stroke

Author

Bitar, Lynn, primary, Uphaus, Timo, additional, Thalman, Carine, additional, Muthuraman, Muthuraman, additional, Gyr, Luzia, additional, Ji, Haichao, additional, Domingues, Micaela, additional, Endle, Heiko, additional, Groppa, Sergiu, additional, Steffen, Falk, additional, Koirala, Nabin, additional, Fan, Wei, additional, Ibanez, Laura, additional, Heitsch, Laura, additional, Cruchaga, Carlos, additional, Lee, Jin-Moo, additional, Kloss, Florian, additional, Bittner, Stefan, additional, Nitsch, Robert, additional, Zipp, Frauke, additional, and Vogt, Johannes, additional

Published
2022
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32. sj-docx-1-tan-10.1177_17562864221142924 – Supplemental material for Comparative effectiveness of natalizumab versus ocrelizumab in multiple sclerosis: a real-world propensity score–matched study

Author

Pape, Katrin, Rolfes, Leoni, Steffen, Falk, Muthuraman, Muthuraman, Korsen, Melanie, Meuth, Sven G., Zipp, Frauke, and Bittner, Stefan

Subjects
FOS: Clinical medicine, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified, 110904 Neurology and Neuromuscular Diseases
Abstract

Supplemental material, sj-docx-1-tan-10.1177_17562864221142924 for Comparative effectiveness of natalizumab versus ocrelizumab in multiple sclerosis: a real-world propensity score–matched study by Katrin Pape, Leoni Rolfes, Falk Steffen, Muthuraman Muthuraman, Melanie Korsen, Sven G. Meuth, Frauke Zipp and Stefan Bittner in Therapeutic Advances in Neurological Disorders

Published
2022
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33. Additional file 1 of Immunoadsorption versus double-dose methylprednisolone in refractory multiple sclerosis relapses

Author

Pfeuffer, Steffen, Rolfes, Leoni, Wirth, Timo, Steffen, Falk, Pawlitzki, Marc, Schulte-Mecklenbeck, Andreas, Gross, Catharina C., Brand, Marcus, Bittner, Stefan, Ruck, Tobias, Klotz, Luisa, Wiendl, Heinz, and Meuth, Sven G.

Abstract

Additional file 1: Table S1. Antibodies used for flow cytometric analysis of PBMC. Table S2. Tabular results for OLINK™ target 48-cytokine screening. Significance testing was performed using Wilcoxon’s paired rank-sum test.

Published
2022
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36. NfL predicts relapse-free progression in a longitudinal multiple sclerosis cohort study

Author

Uphaus, Timo, primary, Steffen, Falk, additional, Muthuraman, Muthuraman, additional, Ripfel, Nina, additional, Fleischer, Vinzenz, additional, Groppa, Sergiu, additional, Ruck, Tobias, additional, Meuth, Sven G., additional, Pul, Refik, additional, Kleinschnitz, Christoph, additional, Ellwardt, Erik, additional, Loos, Julia, additional, Engel, Sinah, additional, Zipp, Frauke, additional, and Bittner, Stefan, additional

Published
2021
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37. Exercise Diminishes Plasma Neurofilament Light Chain and Reroutes the Kynurenine Pathway in Multiple Sclerosis

Author

Joisten, Niklas, Rademacher, Annette, Warnke, Clemens, Proschinger, Sebastian, Schenk, Alexander, Walzik, David, Knoop, Andre, Thevis, Mario, Steffen, Falk, Bittner, Stefan, Gonzenbach, Roman, Kool, Jan, Bloch, Wilhelm, Bansi, Jens, Zimmer, Philipp, Joisten, Niklas, Rademacher, Annette, Warnke, Clemens, Proschinger, Sebastian, Schenk, Alexander, Walzik, David, Knoop, Andre, Thevis, Mario, Steffen, Falk, Bittner, Stefan, Gonzenbach, Roman, Kool, Jan, Bloch, Wilhelm, Bansi, Jens, and Zimmer, Philipp

Abstract

Objective To examine acute (single-bout) and training effects of high-intensity interval training (HIIT) vs standard exercise therapy (moderate continuous training [MCT]) on plasma neurofilament light chain (pNfL) and kynurenine (KYN) pathway of tryptophan degradation metabolites in persons with multiple sclerosis (pwMS). Methods Sixty-nine pwMS (Expanded Disability Status Scale score 3.0-6.0) were randomly assigned to a HIIT or an MCT group. Changes in pNfL and KYN pathway metabolites measured in blood plasma were assessed before, after, and 3 hours after the first training session as well as after the 3-week training intervention. Results Acute exercise reduced pNfL and increased the KYN pathway flux toward the neuroprotective kynurenic acid (KA). Changes in pNfL correlated positively with changes in KA and negatively with the quinolinic acid-to-KA ratio. HIIT consistently led to greater effects than MCT. Following the 3-week training intervention, the KYN pathway was activated in HIIT compared with MCT. Conclusion Future studies and clinical assessments of pNfL should consider acute exercise as confounding factor for measurement reliability. Moreover, exercise-induced KYN pathway rerouting might mediate neuroprotection, potentially underlying the benefits in rehabilitation for pwMS. Classification of Evidence This study provides Class II evidence that acute HIIT diminishes pNfL and increases KA levels, and 3 weeks of HIIT activate the KYN pathway in pwMS.

Published
2021

38. sj-docx-1-tan-10.1177_17562864211051497 – Supplemental material for Association of serum neurofilament light chain levels and neuropsychiatric manifestations in systemic lupus erythematosus

Author

Engel, Sinah, Boedecker, Simone, Marczynski, Paul, Bittner, Stefan, Steffen, Falk, Weinmann, Arndt, Schwarting, Andreas, Zipp, Frauke, Weinmann-Menke, Julia, and Luessi, Felix

Subjects
FOS: Clinical medicine, skin and connective tissue diseases, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified, 110904 Neurology and Neuromuscular Diseases
Abstract

Supplemental material, sj-docx-1-tan-10.1177_17562864211051497 for Association of serum neurofilament light chain levels and neuropsychiatric manifestations in systemic lupus erythematosus by Sinah Engel, Simone Boedecker, Paul Marczynski, Stefan Bittner, Falk Steffen, Arndt Weinmann, Andreas Schwarting, Frauke Zipp, Julia Weinmann-Menke and Felix Luessi in Therapeutic Advances in Neurological Disorders

Published
2021
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39. NfL predicts relapse-free progression in a longitudinal multiple sclerosis cohort study : Serum NfL predicts relapse-free progression

Author

Uphaus, Timo, Steffen, Falk, Muthuraman, Muthuraman, Ripfel, Nina, Fleischer, Vinzenz, Groppa, Sergiu, Ruck, Tobias, Meuth, Sven G., Pul, Refik, Kleinschnitz, Christoph, Ellwardt, Erik, Loos, Julia, Engel, Sinah, Zipp, Frauke, and Bittner, Stefan

Subjects
Medizin
Abstract

Background: Easily accessible biomarkers enabling the identification of those patients with multiple sclerosis (MS) who will accumulate irreversible disability in the long term are essential to guide early therapeutic decisions. We here examine the utility of serum neurofilament light chain (sNfL) for forecasting relapse-free disability progression and conversion to secondary progressive MS (SPMS) in the prospective Neurofilament and longterm outcome in MS (NaloMS) cohort. Methods: The predictive ability of sNfL at Baseline and sNfL follow-up (FU)/ Baseline (BL) ratio with regard to disability progression was assessed within a development cohort (NaloMS, n=196 patients with relapsing-remitting MS (RRMS) or clinically isolated syndrome) and validated with an external independent cohort (Düsseldorf, Essen, n=204). Both relapse-free EDSS-progression (RFP: inflammatory-independent EDSS-increase 12 months prior to FU) and SPMS-transition (minimum EDSS-score of 3.0) were investigated. Findings: During the study period, 17% (n=34) of NaloMS patients suffered from RFP and 14% (n=27) converted to SPMS at FU (validation cohort RFP n=42, SPMS-conversion n=24). sNfL at BL was increased in patients with RFP (10.8 pg/ml (interquartile range (IQR) 7.7-15.0) vs. 7.2 pg/ml (4.5-12.5), p

Published
2021

40. Exercise Diminishes Plasma Neurofilament Light Chain and Reroutes the Kynurenine Pathway in Multiple Sclerosis

Author

Joisten, Niklas, primary, Rademacher, Annette, additional, Warnke, Clemens, additional, Proschinger, Sebastian, additional, Schenk, Alexander, additional, Walzik, David, additional, Knoop, Andre, additional, Thevis, Mario, additional, Steffen, Falk, additional, Bittner, Stefan, additional, Gonzenbach, Roman, additional, Kool, Jan, additional, Bloch, Wilhelm, additional, Bansi, Jens, additional, and Zimmer, Philipp, additional

Published
2021
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46. sj-pdf-4-mso-10.1177_2055217320936318 - Supplemental material for Supplementary medication in multiple sclerosis: Real-world experience and potential interference with neurofilament light chain measurement

Author

Pape, Katrin, Steffen, Falk, Zipp, Frauke, and Bittner, Stefan

Subjects
FOS: Clinical medicine, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract

Supplemental material, sj-pdf-4-mso-10.1177_2055217320936318 for Supplementary medication in multiple sclerosis: Real-world experience and potential interference with neurofilament light chain measurement by Katrin Pape, Falk Steffen, Frauke Zipp and Stefan Bittner in Multiple Sclerosis Journal – Experimental, Translational and Clinical

Published
2020
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47. sj-pdf-8-mso-10.1177_2055217320936318 - Supplemental material for Supplementary medication in multiple sclerosis: Real-world experience and potential interference with neurofilament light chain measurement

Author

Pape, Katrin, Steffen, Falk, Zipp, Frauke, and Bittner, Stefan

Subjects
FOS: Clinical medicine, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract

Supplemental material, sj-pdf-8-mso-10.1177_2055217320936318 for Supplementary medication in multiple sclerosis: Real-world experience and potential interference with neurofilament light chain measurement by Katrin Pape, Falk Steffen, Frauke Zipp and Stefan Bittner in Multiple Sclerosis Journal – Experimental, Translational and Clinical

Published
2020
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48. sj-pdf-6-mso-10.1177_2055217320936318 - Supplemental material for Supplementary medication in multiple sclerosis: Real-world experience and potential interference with neurofilament light chain measurement

Author

Pape, Katrin, Steffen, Falk, Zipp, Frauke, and Bittner, Stefan

Subjects
FOS: Clinical medicine, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract

Supplemental material, sj-pdf-6-mso-10.1177_2055217320936318 for Supplementary medication in multiple sclerosis: Real-world experience and potential interference with neurofilament light chain measurement by Katrin Pape, Falk Steffen, Frauke Zipp and Stefan Bittner in Multiple Sclerosis Journal – Experimental, Translational and Clinical

Published
2020
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49. sj-pdf-3-mso-10.1177_2055217320936318 - Supplemental material for Supplementary medication in multiple sclerosis: Real-world experience and potential interference with neurofilament light chain measurement

Author

Pape, Katrin, Steffen, Falk, Zipp, Frauke, and Bittner, Stefan

Subjects
FOS: Clinical medicine, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract

Supplemental material, sj-pdf-3-mso-10.1177_2055217320936318 for Supplementary medication in multiple sclerosis: Real-world experience and potential interference with neurofilament light chain measurement by Katrin Pape, Falk Steffen, Frauke Zipp and Stefan Bittner in Multiple Sclerosis Journal – Experimental, Translational and Clinical

Published
2020
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50. sj-pdf-1-mso-10.1177_2055217320936318 - Supplemental material for Supplementary medication in multiple sclerosis: Real-world experience and potential interference with neurofilament light chain measurement

Author

Pape, Katrin, Steffen, Falk, Zipp, Frauke, and Bittner, Stefan

Subjects
FOS: Clinical medicine, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract

Supplemental material, sj-pdf-1-mso-10.1177_2055217320936318 for Supplementary medication in multiple sclerosis: Real-world experience and potential interference with neurofilament light chain measurement by Katrin Pape, Falk Steffen, Frauke Zipp and Stefan Bittner in Multiple Sclerosis Journal – Experimental, Translational and Clinical

Published
2020
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