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3. Translational value of choroid plexus imaging for tracking neuroinflammation in mice and humans

Author

Fleischer, Vinzenz, Gonzalez-Escamilla, Gabriel, Ciolac, Dumitru, Albrecht, Philipp, Küry, Patrick, Gruchot, Joel, Dietrich, Michael, Hecker, Christina, Müntefering, Thomas, Bock, Stefanie, Oshaghi, Mohammadsaleh, Radetz, Angela, Cerina, Manuela, Krämer, Julia, Wachsmuth, Lydia, Faber, Cornelius, Lassmann, Hans, Ruck, Tobias, Meuth, Sven G., Muthuraman, Muthuraman, and Groppa, Sergiu

Published
2021

6. Safety and efficacy of erythropoietin for the treatment of patients with optic neuritis (TONE): a randomised, double-blind, multicentre, placebo-controlled study

Author

Albrecht, Philipp, Aktas, Orhan, Beck, Anna, Beckmann, Anke, Beisse, Flemming, Berthele, Achim, Bönig, Lena, Diem, Ricarda, Elflein, Heike, Fitzner, Dirk, Fleischer, Vinzenz, Gingele, Stefan, Grotejohann, Birgit, Guthoff, Tanja, Guthoff, Rainer, Hartmann, Kathrin, Hassenstein, Andrea, Heesen, Christoph, Hein, Katharina, Heinrich, Sven P., Hufendiek, Karsten, Hug, Martin J., Huhn, Konstantin, Hümmert, Martin W., Ihorst, Gabriele, Klopfer, Matthias, Kruse, Friedrich E., Küchlin, Sebastian, Kümpfel, Tania, Lagrèze, Wolf A., Linker, Ralf A., Lorenz, Katrin, Molnár, Fanni E., Mulazzani, Elisabeth, Müller, Marcus, Nickel, Florian T., Noll, Marion, Pielen, Amelie, Pitz, Susanne, Rauer, Sebastian, Reich, Michael, Rosenkranz, Sina, Schwenkenbecher, Philipp, Siller, Nelly, Skripuletz, Thomas, Stangel, Martin, Stellmann, Jan-Patrick, Stürner, Klarissa, Sühs, Kurt-Wolfram, Ungewiss, Judith, Uphaus, Timo, van Oterendorp, Christian, Volkmann, Martin, Wabbels, Bettina, Wilhelm, Helmut, Wolf, Sebastian, Wörner, Michael, Ziemann, Ulf, Zipp, Frauke, Lagrèze, Wolf A, Heinrich, Sven P, and Hug, Martin J

Published
2021
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7. Choroid plexus enlargement in acute neuroinflammation is tightly interrelated to the tyrosine receptor signalling

Author

Luessi, Felix, primary, Schiffer, Julia, additional, Gonzalez-Escamilla, Gabriel, additional, Fleischer, Vinzenz, additional, Engel, Sinah, additional, Ciolac, Dumitru, additional, Koeck, Thomas, additional, Wild, Philipp S., additional, Gruchot, Joel, additional, Ruck, Tobias, additional, Othmann, Ahmed, additional, Bittner, Stefan, additional, Meuth, Sven G., additional, Zipp, Frauke, additional, Stueve, Olaf, additional, and Groppa, Sergiu, additional

Published
2024
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10. Multiple sclerosis endophenotypes identified by high-dimensional blood signatures are associated with distinct disease trajectories.

Author

Gross, Catharina C., Schulte-Mecklenbeck, Andreas, Steinberg, Olga V., Wirth, Timo, Lauks, Sarah, Bittner, Stefan, Schindler, Patrick, Baranzini, Sergio E., Groppa, Sergiu, Bellmann-Strobl, Judith, Bünger, Nora, Chien, Claudia, Dawin, Eva, Eveslage, Maria, Fleischer, Vinzenz, Gonzalez-Escamilla, Gabriel, Gisevius, Barbara, Haas, Jürgen, Kerschensteiner, Martin, and Kirstein, Lucienne

Subjects
AUTOIMMUNE diseases, MULTIPLE sclerosis, MONONUCLEAR leukocytes, BLOOD diseases
Abstract

One of the biggest challenges in managing multiple sclerosis is the heterogeneity of clinical manifestations and progression trajectories. It still remains to be elucidated whether this heterogeneity is reflected by discrete immune signatures in the blood as a surrogate of disease pathophysiology. Accordingly, individualized treatment selection based on immunobiological principles is still not feasible. Using two independent multicentric longitudinal cohorts of patients with early multiple sclerosis (n = 309 discovery and n = 232 validation), we were able to identify three distinct peripheral blood immunological endophenotypes by a combination of high-dimensional flow cytometry and serum proteomics, followed by unsupervised clustering. Longitudinal clinical and paraclinical follow-up data collected for the cohorts revealed that these endophenotypes were associated with disease trajectories of inflammation versus early structural damage. Investigating the capacity of immunotherapies to normalize endophenotype-specific immune signatures revealed discrete effect sizes as illustrated by the limited effect of interferon-β on endophenotype 3–related immune signatures. Accordingly, patients who fell into endophenotype 3 subsequently treated with interferon-β exhibited higher disease progression and MRI activity over a 4-year follow-up compared with treatment with other therapies. We therefore propose that ascertaining a patient's blood immune signature before immunomodulatory treatment initiation may facilitate prediction of clinical disease trajectories and enable personalized treatment decisions based on pathobiological principles. Editor's summary: The autoimmune disease multiple sclerosis (MS) is a highly heterogeneous disease with many different treatment options. However, it is not clear whether certain features of MS are associated with distinct immune signatures or would benefit from particular therapies. Here, Gross et al. used peripheral blood mononuclear cells and serum collected from two independent cohorts of patients with MS to identify three endophenotypes of the disease. These peripheral blood immune signatures distinguished patients with distinct clinical disease trajectories and efficacy of interferon-β treatment. These data suggest that peripheral blood analysis could be used to guide personalized treatment regimens for patients with MS. —Courtney Malo [ABSTRACT FROM AUTHOR]

Published
2024
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11. Assessing treatment response to oral drugs for multiple sclerosis in real-world setting: a MAGNIMS Study.

Author

Ruggieri, Serena, Prosperini, Luca, Al-Araji, Sarmad, Annovazzi, Pietro Osvaldo, Bisecco, Alvino, Ciccarelli, Olga, De Stefano, Nicola, Filippi, Massimo, Fleischer, Vinzenz, Evangelou, Nikos, Enzinger, Christian, Gallo, Antonio, Garjani, Afagh, Groppa, Sergiu, Haggiag, Shalom, Khalil, Michael, Lucchini, Matteo, Mirabella, Massimiliano, Montalban, Xavier, and Pozzilli, Carlo

Subjects
MULTIPLE sclerosis, ORAL medication, ORAL drug administration, MEDICAL sciences, PROGNOSIS
Published
2024
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12. Prognostic value of single-subject grey matter networks in early multiple sclerosis.

Author

Fleischer, Vinzenz, Gonzalez-Escamilla, Gabriel, Pareto, Deborah, Rovira, Alex, Sastre-Garriga, Jaume, Sowa, Piotr, Høgestøl, Einar A, Harbo, Hanne F, Bellenberg, Barbara, Lukas, Carsten, Ruggieri, Serena, Gasperini, Claudio, Uher, Tomas, Vaneckova, Manuela, Bittner, Stefan, Othman, Ahmed E, Collorone, Sara, Toosy, Ahmed T, Meuth, Sven G, and Zipp, Frauke

Subjects
*PROGNOSIS, *MULTIPLE sclerosis, *WHITE matter (Nerve tissue), *MAGNETIC resonance imaging, *LARGE-scale brain networks
Abstract

The identification of prognostic markers in early multiple sclerosis (MS) is challenging and requires reliable measures that robustly predict future disease trajectories. Ideally, such measures should make inferences at the individual level to inform clinical decisions. This study investigated the prognostic value of longitudinal structural networks to predict 5-year Expanded Disability Status Scale (EDSS) progression in patients with relapsing-remitting MS (RRMS). We hypothesized that network measures, derived from MRI, outperform conventional MRI measurements at identifying patients at risk of developing disability progression. This longitudinal, multicentre study within the Magnetic Resonance Imaging in MS (MAGNIMS) network included 406 patients with RRMS (mean age = 35.7 ± 9.1 years) followed up for 5 years (mean follow-up = 5.0 ± 0.6 years). EDSS was determined to track disability accumulation. A group of 153 healthy subjects (mean age = 35.0 ± 10.1 years) with longitudinal MRI served as controls. All subjects underwent MRI at baseline and again 1 year after baseline. Grey matter atrophy over 1 year and white matter lesion load were determined. A single-subject brain network was reconstructed from T1-weighted scans based on grey matter atrophy measures derived from a statistical parameter mapping-based segmentation pipeline. Key topological measures, including network degree, global efficiency and transitivity, were calculated at single-subject level to quantify network properties related to EDSS progression. Areas under receiver operator characteristic (ROC) curves were constructed for grey matter atrophy and white matter lesion load, and the network measures and comparisons between ROC curves were conducted. The applied network analyses differentiated patients with RRMS who experience EDSS progression over 5 years through lower values for network degree [H(2) = 30.0, P < 0.001] and global efficiency [H(2) = 31.3, P < 0.001] from healthy controls but also from patients without progression. For transitivity, the comparisons showed no difference between the groups [H(2) = 1.5, P = 0.474]. Most notably, changes in network degree and global efficiency were detected independent of disease activity in the first year. The described network reorganization in patients experiencing EDSS progression was evident in the absence of grey matter atrophy. Network degree and global efficiency measurements demonstrated superiority of network measures in the ROC analyses over grey matter atrophy and white matter lesion load in predicting EDSS worsening (all P -values < 0.05). Our findings provide evidence that grey matter network reorganization over 1 year discloses relevant information about subsequent clinical worsening in RRMS. Early grey matter restructuring towards lower network efficiency predicts disability accumulation and outperforms conventional MRI predictors. [ABSTRACT FROM AUTHOR]

Published
2024
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13. Assessing treatment response to oral drugs for multiple sclerosis in real-world setting: a MAGNIMS Study

Author

Ruggieri, Serena, primary, Prosperini, Luca, additional, Al-Araji, Sarmad, additional, Annovazzi, Pietro Osvaldo, additional, Bisecco, Alvino, additional, Ciccarelli, Olga, additional, De Stefano, Nicola, additional, Filippi, Massimo, additional, Fleischer, Vinzenz, additional, Evangelou, Nikos, additional, Enzinger, Christian, additional, Gallo, Antonio, additional, Garjani, Afagh, additional, Groppa, Sergiu, additional, Haggiag, Shalom, additional, Khalil, Michael, additional, Lucchini, Matteo, additional, Mirabella, Massimiliano, additional, Montalban, Xavier, additional, Pozzilli, Carlo, additional, Preziosa, Paolo, additional, Río, Jordi, additional, Rocca, Maria A, additional, Rovira, Alex, additional, Stromillo, Maria L, additional, Zaffaroni, Mauro, additional, Tortorella, Carla, additional, and Gasperini, Claudio, additional

Published
2023
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14. Prognostic value of single-subject grey matter networks in early multiple sclerosis

Author

Fleischer, Vinzenz, primary, Gonzalez-Escamilla, Gabriel, additional, Pareto, Deborah, additional, Rovira, Alex, additional, Sastre-Garriga, Jaume, additional, Sowa, Piotr, additional, Høgestøl, Einar A, additional, Harbo, Hanne F, additional, Bellenberg, Barbara, additional, Lukas, Carsten, additional, Ruggieri, Serena, additional, Gasperini, Claudio, additional, Uher, Tomas, additional, Vaneckova, Manuela, additional, Bittner, Stefan, additional, Othman, Ahmed E, additional, Collorone, Sara, additional, Toosy, Ahmed T, additional, Meuth, Sven G, additional, Zipp, Frauke, additional, Barkhof, Frederik, additional, Ciccarelli, Olga, additional, and Groppa, Sergiu, additional

Published
2023
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18. Diffusion-based structural connectivity patterns of multiple sclerosis phenotypes

Author

Martinez-Heras, Eloy, primary, Solana, Elisabeth, additional, Vivó, Francesc, additional, Lopez-Soley, Elisabet, additional, Calvi, Alberto, additional, Alba-Arbalat, Salut, additional, Schoonheim, Menno M, additional, Strijbis, Eva M, additional, Vrenken, Hugo, additional, Barkhof, Frederik, additional, Rocca, Maria A, additional, Filippi, Massimo, additional, Pagani, Elisabetta, additional, Groppa, Sergiu, additional, Fleischer, Vinzenz, additional, Dineen, Robert A, additional, Bellenberg, Barbara, additional, Lukas, Carsten, additional, Pareto, Deborah, additional, Rovira, Alex, additional, Sastre-Garriga, Jaume, additional, Collorone, Sara, additional, Prados, Ferran, additional, Toosy, Ahmed, additional, Ciccarelli, Olga, additional, Saiz, Albert, additional, Blanco, Yolanda, additional, and Llufriu, Sara, additional

Published
2023
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19. Identification of multiple sclerosis endophenotypes by high dimensional blood signatures associated with distinct disease trajectories (P1-3.008)

Author

Gross, Catharina C., primary, Schulte-Mecklenbeck, Andreas, additional, Steinberg, Olga V., additional, Wirth, Timo, additional, Lauks, Sarah, additional, Baranzini, Sergio E., additional, Bittner, Stefan, additional, Bellmann-Strobl, Judith, additional, Bünger, Nora, additional, Eilers, Eva, additional, Eveslage, Maria, additional, Fleischer, Vinzenz, additional, Gisevius, Barbara, additional, Groppa, Sergiu, additional, Haas, Jürgen, additional, Kerschensteiner, Martin, additional, Kirstein, Lucienne, additional, Korsukewitz, Catharina, additional, Lohmann, Lisa, additional, Lünemann, Jan, additional, Lüssi, Felix, additional, Hörste, Gerd Meyerzu, additional, Motte, Jeremias, additional, Ruck, Tobias, additional, Schwab, Nicholas, additional, Meuth, Sven G., additional, Paul, Friedemann, additional, Wildemann, Brigitte, additional, Kümpfel, Tania, additional, Gold, Ralf, additional, Zipp, Frauke, additional, Klotz, Luisa, additional, and Wiendl, Heinz, additional

Published
2023
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20. Assessing treatment response to oral drugs for multiple sclerosis in real-world setting: a MAGNIMS Study

Author

Ruggieri, Serena, Prosperini, Luca, Al-Araji, Sarmad, Annovazzi, Pietro Osvaldo, Bisecco, Alvino, Ciccarelli, Olga, De Stefano, Nicola, Filippi, Massimo, Fleischer, Vinzenz, Evangelou, Niko, Enzinger, Christian, Gallo, Antonio, Garjani, Afagh, Groppa, Sergiu, Haggiag, Shalom, Khalil, Michael, Lucchini, Matteo, Mirabella, Massimiliano, Montalban, Xavier, Pozzilli, Carlo, Preziosa, Paolo, Río, Jordi, Rocca, Maria A, Rovira, Alex, Stromillo, Maria L, Zaffaroni, Mauro, Tortorella, Carla, Gasperini, Claudio, Lucchini, Matteo (ORCID:0000-0002-0447-2297), Mirabella, Massimiliano (ORCID:0000-0002-7783-114X), Ruggieri, Serena, Prosperini, Luca, Al-Araji, Sarmad, Annovazzi, Pietro Osvaldo, Bisecco, Alvino, Ciccarelli, Olga, De Stefano, Nicola, Filippi, Massimo, Fleischer, Vinzenz, Evangelou, Niko, Enzinger, Christian, Gallo, Antonio, Garjani, Afagh, Groppa, Sergiu, Haggiag, Shalom, Khalil, Michael, Lucchini, Matteo, Mirabella, Massimiliano, Montalban, Xavier, Pozzilli, Carlo, Preziosa, Paolo, Río, Jordi, Rocca, Maria A, Rovira, Alex, Stromillo, Maria L, Zaffaroni, Mauro, Tortorella, Carla, Gasperini, Claudio, Lucchini, Matteo (ORCID:0000-0002-0447-2297), and Mirabella, Massimiliano (ORCID:0000-0002-7783-114X)

Abstract

Background: The assessment of treatment response is a crucial step for patients with relapsing-remitting multiple sclerosis on disease-modifying therapies (DMTs). We explored whether a scoring system developed within the MAGNIMS (MRI in Multiple Sclerosis) network to evaluate treatment response to injectable drugs can be adopted also to oral DMTs. Methods: A multicentre dataset of 1200 patients who started three oral DMTs (fingolimod, teriflunomide and dimethyl fumarate) was collected within the MAGNIMS network. Disease activity after the first year was classified by the 'MAGNIMS' score based on the combination of relapses (0-≥2) and/or new T2 lesions (<3 or ≥3) on brain MRI. We explored the association of this score with the following 3-year outcomes: (1) confirmed disability worsening (CDW); (2) treatment failure (TFL); (3) relapse count between years 1 and 3. The additional value of contrast-enhancing lesions (CELs) and lesion location was explored. Results: At 3 years, 160 patients experienced CDW: 12% of them scored '0' (reference), 18% scored '1' (HR=1.82, 95% CI 1.20 to 2.76, p=0.005) and 37% scored '2' (HR=2.74, 95% CI 1.41 to 5.36, p=0.003) at 1 year. The analysis of other outcomes provided similar findings. Considering the location of new T2 lesions (supratentorial vs infratentorial/spinal cord) and the presence of CELs improved the prediction of CDW and TFL, respectively, in patients with minimal MRI activity alone (one or two new T2 lesions). Conclusions: Early relapses and substantial MRI activity in the first year of treatment are associated with worse short-term outcomes in patients treated with some of the oral DMTs.

Published
2023

21. Myelination- and immune-mediated MR-based brain network correlates

Author

Cerina, Manuela, Muthuraman, Muthuraman, Gallus, Marco, Koirala, Nabin, Dik, Andre, Wachsmuth, Lydia, Hundehege, Petra, Schiffler, Patrick, Tenberge, Jan-Gerd, Fleischer, Vinzenz, Gonzalez-Escamilla, Gabriel, Narayanan, Venu, Krämer, Julia, Faber, Cornelius, Budde, Thomas, Groppa, Sergiu, and Meuth, Sven G.

Published
2020
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27. Factors associated with depressive mood at the onset of multiple sclerosis - an analysis of 781 patients of the German NationMS cohort

Author

Salmen, Anke, primary, Hoepner, Robert, additional, Fleischer, Vinzenz, additional, Heldt, Milena, additional, Gisevius, Barbara, additional, Motte, Jeremias, additional, Ruprecht, Klemens, additional, Schneider, Ruth, additional, Fisse, Anna Lena, additional, Grüter, Thomas, additional, Lukas, Carsten, additional, Berthele, Achim, additional, Giglhuber, Katrin, additional, Flaskamp, Martina, additional, Mühlau, Mark, additional, Kirschke, Jan, additional, Bittner, Stefan, additional, Groppa, Sergiu, additional, Lüssi, Felix, additional, Bayas, Antonios, additional, Meuth, Sven, additional, Heesen, Cristoph, additional, Trebst, Corinna, additional, Wildemann, Brigitte, additional, Then Bergh, Florian, additional, Antony, Gisela, additional, Kümpfel, Tania, additional, Paul, Friedemann, additional, Nischwitz, Sandra, additional, Tumani, Hayrettin, additional, Zettl, Uwe, additional, Hemmer, Bernhard, additional, Wiendl, Heinz, additional, Zipp, Frauke, additional, and Gold, Ralf, additional

Published
2023
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38. Altered grey matter integrity and network vulnerability relate to epilepsy occurrence in patients with multiple sclerosis

Author

Ciolac, Dumitru, primary, Gonzalez‐Escamilla, Gabriel, additional, Winter, Yaroslav, additional, Melzer, Nico, additional, Luessi, Felix, additional, Radetz, Angela, additional, Fleischer, Vinzenz, additional, Groppa, Stanislav A., additional, Kirsch, Michael, additional, Bittner, Stefan, additional, Zipp, Frauke, additional, Muthuraman, Muthuraman, additional, Meuth, Sven G., additional, Grothe, Matthias, additional, and Groppa, Sergiu, additional

Published
2022
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39. Subcortical volumes as early predictors of fatigue in multiple sclerosis

Author

Fleischer, Vinzenz, Ciolac, Dumitru, Gonzalez-Escamilla, Gabriel, Grothe, Matthias, Strauss, Sebastian, Molina Galindo, Lara S, Radetz, Angela, Salmen, Anke, Lukas, Carsten, Klotz, Luisa, Meuth, Sven G, Bayas, Antonios, Paul, Friedemann, Hartung, Hans-Peter, Heesen, Christoph, Stangel, Martin, Wildemann, Brigitte, Bergh, Florian Then, Tackenberg, Bj��rn, K��mpfel, Tania, Zettl, Uwe K, Knop, Matthias, Tumani, Hayrettin, Wiendl, Heinz, Gold, Ralf, Bittner, Stefan, Zipp, Frauke, Groppa, Sergiu, and Muthuraman, Muthuraman

Subjects
Adult, Male, Multiple Sclerosis, 610 Medizin, 610 Medicine & health, Cohort Studies, Young Adult, Predictive Value of Tests, Pons, 610 Medical sciences, Humans, Longitudinal Studies, ddc:610, Gray Matter, Fatigue, Putamen, Brain, Middle Aged, Prognosis, Magnetic Resonance Imaging, Cross-Sectional Studies, Neurology, Female, Neurology (clinical), Nerve Net, Function and Dysfunction of the Nervous System, Demyelinating Diseases, Follow-Up Studies
Abstract

OBJECTIVE Fatigue is a frequent and severe symptom in multiple sclerosis (MS), but its pathophysiological origin remains incompletely understood. We aimed to examine the predictive value of subcortical gray matter volumes for fatigue severity at disease onset and after four years by applying structural equation modeling (SEM). METHODS This multi-center cohort study included 601 treatment-naive MS patients after the first demyelinating event. All patients underwent a standardized 3T MRI protocol. A subgroup of 230 patients with available clinical follow-up data after four years was also analyzed. Associations of subcortical volumes (included into SEM) with MS-related fatigue were studied regarding their predictive value. In addition, subcortical regions that have a central role in the brain network (hubs) were determined through structural covariance network (SCN) analysis. RESULTS Predictive causal modeling identified volumes of the caudate (s [standardized path coefficient]=0.763, p=0.003 [left]; s=0.755, p=0.006 [right]), putamen (s=0.614, p=0.002 [left]; s=0.606, p=0.003 [right]) and pallidum (s=0.606, p=0.012 [left]; s=0.606, p=0.012 [right]) as prognostic factors for fatigue severity in the cross-sectional cohort. Moreover, the volume of the pons was additionally predictive for fatigue severity in the longitudinal cohort (s=0.605, p=0.013). In the SCN analysis, network hubs in patients with fatigue worsening were detected in the putamen (p=0.008 [left]; p=0.007 [right]) and pons (p=0.0001). INTERPRETATION We unveiled predictive associations of specific subcortical gray matter volumes with fatigue in an early and initially untreated MS cohort. The colocalization of these subcortical structures with network hubs suggests an early role of these brain regions in terms of fatigue evolution. This article is protected by copyright. All rights reserved.

Published
2022

40. Additional file 1 of Network alterations underlying anxiety symptoms in early multiple sclerosis

Author

Ellwardt, Erik, Muthuraman, Muthuraman, Gonzalez-Escamilla, Gabriel, Chirumamilla, Venkata Chaitanya, Luessi, Felix, Bittner, Stefan, Zipp, Frauke, Groppa, Sergiu, and Fleischer, Vinzenz

Subjects
nervous system
Abstract

Additional file 1: Table S1. Clinical data of the additional multiple sclerosis patients in the TMS–HD-EEG study. Table S2. Cortical volume changes over 2 years (ROI-wise). Table S3. Subcortical volume changes over 2 years. Table S4. Association between cortical atrophy over 2 years and HADS-A (anxiety) after 2 years. Table S5. Association between subcortical atrophy over 2 years and HADS-A (anxiety) after 2 years. Table S6. Correlations (r) between connectivity strength and volumes (prefrontal cortex, hippocampus and amygdala). Figure S1. Heart rate of multiple sclerosis patients and healthy controls during TMS–HD-EEG study. Figure S2. Connectivity/coherence. Connectivity and coherence between prefrontal cortex, amygdala and hippocampus at rest and during threat processing in the TMS–HD-EEG study.

Published
2022
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42. Safety and efficacy of erythropoietin for the treatment of patients with optic neuritis (TONE): a randomised, double-blind, multicentre, placebo-controlled study

Author

Lagrèze, Wolf A, primary, Küchlin, Sebastian, additional, Ihorst, Gabriele, additional, Grotejohann, Birgit, additional, Beisse, Flemming, additional, Volkmann, Martin, additional, Heinrich, Sven P, additional, Albrecht, Philipp, additional, Ungewiss, Judith, additional, Wörner, Michael, additional, Hug, Martin J, additional, Wolf, Sebastian, additional, Diem, Ricarda, additional, Aktas, Orhan, additional, Beck, Anna, additional, Beckmann, Anke, additional, Berthele, Achim, additional, Bönig, Lena, additional, Elflein, Heike, additional, Fitzner, Dirk, additional, Fleischer, Vinzenz, additional, Gingele, Stefan, additional, Guthoff, Tanja, additional, Guthoff, Rainer, additional, Hartmann, Kathrin, additional, Hassenstein, Andrea, additional, Heesen, Christoph, additional, Hein, Katharina, additional, Heinrich, Sven P., additional, Hufendiek, Karsten, additional, Hug, Martin J., additional, Huhn, Konstantin, additional, Hümmert, Martin W., additional, Klopfer, Matthias, additional, Kruse, Friedrich E., additional, Kümpfel, Tania, additional, Lagrèze, Wolf A., additional, Linker, Ralf A., additional, Lorenz, Katrin, additional, Molnár, Fanni E., additional, Mulazzani, Elisabeth, additional, Müller, Marcus, additional, Nickel, Florian T., additional, Noll, Marion, additional, Pielen, Amelie, additional, Pitz, Susanne, additional, Rauer, Sebastian, additional, Reich, Michael, additional, Rosenkranz, Sina, additional, Schwenkenbecher, Philipp, additional, Siller, Nelly, additional, Skripuletz, Thomas, additional, Stangel, Martin, additional, Stellmann, Jan-Patrick, additional, Stürner, Klarissa, additional, Sühs, Kurt-Wolfram, additional, Uphaus, Timo, additional, van Oterendorp, Christian, additional, Wabbels, Bettina, additional, Wilhelm, Helmut, additional, Ziemann, Ulf, additional, and Zipp, Frauke, additional

Published
2021
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44. 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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45. 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

46. Sex-specific signatures of intrinsic hippocampal networks and regional integrity underlying cognitive status in multiple sclerosis

Author

Ciolac, Dumitru, primary, Gonzalez-Escamilla, Gabriel, additional, Radetz, Angela, additional, Fleischer, Vinzenz, additional, Person, Maren, additional, Johnen, Andreas, additional, Landmeyer, Nils C, additional, Krämer, Julia, additional, Muthuraman, Muthuraman, additional, Meuth, Sven G, additional, and Groppa, Sergiu, additional

Published
2021
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48. Additional file 5 of Myelination- and immune-mediated MR-based brain network correlates

Author

Cerina, Manuela, Muthuraman, Muthuraman, Gallus, Marco, Nabin Koirala, Dik, Andre, Wachsmuth, Lydia, Hundehege, Petra, Schiffler, Patrick, Jan-Gerd Tenberge, Fleischer, Vinzenz, Gonzalez-Escamilla, Gabriel, Venu Narayanan, Krämer, Julia, Faber, Cornelius, Budde, Thomas, Groppa, Sergiu, and Meuth, Sven G.

Subjects
mental disorders
Abstract

Additional file 5: Figure S5. The amyloid precursor protein (APP) accumulation upon de- and remyelination in frontal neocortical regions. Exemplary pictures show APP staining in the lower layers of frontal neocortical regions in control conditions (left), at 6 weeks after starting the cuprizone diet (cupri 6 weeks – full demyelination, middle), and at full remyelination 6 weeks after reintroduction of normal food (right). Note that an increase of positive cells, indicating an accumulation of APP in the neuronal soma, occurred slowly at the onset of the cuprizone diet to reach a significant threshold at remyelinating phases. On the right, bar graphs show the number of APP positive cells (cells/mm2) in Cx.

Published
2020
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49. Additional file 6 of Myelination- and immune-mediated MR-based brain network correlates

Author

Cerina, Manuela, Muthuraman, Muthuraman, Gallus, Marco, Nabin Koirala, Dik, Andre, Wachsmuth, Lydia, Hundehege, Petra, Schiffler, Patrick, Jan-Gerd Tenberge, Fleischer, Vinzenz, Gonzalez-Escamilla, Gabriel, Venu Narayanan, Krämer, Julia, Faber, Cornelius, Budde, Thomas, Groppa, Sergiu, and Meuth, Sven G.

Abstract

Additional file 6: Figure S6. Exploratory and grooming behavior were altered by cuprizone diet and its withdrawn. (a) Bar graph showing quantification of vertical exploratory behavior. Animals show a significant increase in comparison to control 2- and 6 weeks after the beginning of the diet. (b) Bar graph showing the quantification of grooming behavior. The latter is often considered a indicator of stress levels I rodents and here it is significantly decreased, in comparison to control, in almost all experimental groups. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001.

Published
2020
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50. Additional file 2 of Myelination- and immune-mediated MR-based brain network correlates

Author

Cerina, Manuela, Muthuraman, Muthuraman, Gallus, Marco, Nabin Koirala, Dik, Andre, Wachsmuth, Lydia, Hundehege, Petra, Schiffler, Patrick, Jan-Gerd Tenberge, Fleischer, Vinzenz, Gonzalez-Escamilla, Gabriel, Venu Narayanan, Krämer, Julia, Faber, Cornelius, Budde, Thomas, Groppa, Sergiu, and Meuth, Sven G.

Abstract

Additional file 2: Figure S2. Representation of technical and biological replicates for histological evaluation of PLP intensity, astrocytosis and microglial activation in the Cx. (a) Scatter plots and graphs show the variability of the data acquired and used for histological evaluation on myelin intensity by using the specific marker PLP in the cortex (upper panel). (b) Scatter plots and graphs show the variability of the data acquired and used for histological evaluation of the number of astrocytes by using the specific marker GFAP in the cortex (mid panel). Simplified bar graphs are shown in the main figures.

Published
2020
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