TY - JOUR A1 - Brandt, Alexander U. A1 - Zimmermann, Hanna A1 - Kaufhold, Falko A1 - Promesberger, Julia A1 - Schippling, Sven A1 - Finis, David A1 - Aktas, Orhan A1 - Geis, Christian A1 - Ringelstein, Marius A1 - Ringelstein, E. Bernd A1 - Hartung, Hans-Peter A1 - Paul, Friedemann A1 - Kleffner, Ilka A1 - Dörr, Jan T1 - Patterns of Retinal Damage Facilitate Differential Diagnosis between Susac Syndrome and MS JF - PLoS One N2 - Susac syndrome, a rare but probably underdiagnosed combination of encephalopathy, hearing loss, and visual deficits due to branch retinal artery occlusion of unknown aetiology has to be considered as differential diagnosis in various conditions. Particularly, differentiation from multiple sclerosis is often challenging since both clinical presentation and diagnostic findings may overlap. Optical coherence tomography is a powerful and easy to perform diagnostic tool to analyse the morphological integrity of retinal structures and is increasingly established to depict characteristic patterns of retinal pathology in multiple sclerosis. Against this background we hypothesised that differential patterns of retinal pathology facilitate a reliable differentiation between Susac syndrome and multiple sclerosis. In this multicenter cross-sectional observational study optical coherence tomography was performed in nine patients with a definite diagnosis of Susac syndrome. Data were compared with age-, sex-, and disease duration-matched relapsing remitting multiple sclerosis patients with and without a history of optic neuritis, and with healthy controls. Using generalised estimating equation models, Susac patients showed a significant reduction in either or both retinal nerve fibre layer thickness and total macular volume in comparison to both healthy controls and relapsing remitting multiple sclerosis patients. However, in contrast to the multiple sclerosis patients this reduction was not distributed over the entire scanning area but showed a distinct sectorial loss especially in the macular measurements. We therefore conclude that patients with Susac syndrome show distinct abnormalities in optical coherence tomography in comparison to multiple sclerosis patients. These findings recommend optical coherence tomography as a promising tool for differentiating Susac syndrome from MS. KW - optical coherence tomography KW - vasculopathy KW - artery occlusion KW - hearing loss KW - microangiopathy KW - brain KW - endotheliopathy KW - antibodies KW - multiple-sclerosis KW - retinocochleocerebral Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134013 VL - 7 IS - 6 ER - TY - JOUR A1 - Meyer zu Hörste, Gerd A1 - Cordes, Steffen A1 - Mausberg, Anne K. A1 - Zozulya, Alla L. A1 - Wessig, Carsten A1 - Sparwasser, Tim A1 - Mathys, Christian A1 - Wiendl, Heinz A1 - Hartung, Hans-Peter A1 - Kieseier, Bernd C. T1 - FoxP3+Regulatory T Cells Determine Disease Severity in Rodent Models of Inflammatory Neuropathies JF - PLOS ONE N2 - Inflammatory neuropathies represent disabling human autoimmune disorders with considerable disease variability. Animal models provide insights into defined aspects of their disease pathogenesis. Forkhead box P3 (FoxP3)+ regulatory T lymphocytes (Treg) are anti-inflammatory cells that maintain immune tolerance and counteract tissue damage in a variety of immune-mediated disorders. Dysfunction or a reduced frequency of Tregs have been associated with different human autoimmune disorders. We here analyzed the functional relevance of Tregs in determining disease manifestation and severity in murine models of autoimmune neuropathies. We took advantage of the DEREG mouse system allowing depletion of Treg with high specificity as well as anti-CD25 directed antibodies to deplete Tregs in mice in actively induced experimental autoimmune neuritis (EAN). Furthermore antibody-depletion was performed in an adoptive transfer model of chronic neuritis. Early Treg depletion increased clinical EAN severity both in active and adoptive transfer chronic neuritis. This was accompanied by increased proliferation of myelin specific T cells and histological signs of peripheral nerve inflammation. Late stage Treg depletion after initial disease manifestation however did not exacerbate inflammatory neuropathy symptoms further. We conclude that Tregs determine disease severity in experimental autoimmune neuropathies during the initial priming phase, but have no major disease modifying function after disease manifestation. Potential future therapeutic approaches targeting Tregs should thus be performed early in inflammatory neuropathies. KW - Guillain-Barre-Syndrome KW - regulatory cells KW - C57BL/6 mice KW - demyelinating polyradiculoneuropathy KW - cytokines KW - pathogenesis KW - polyneuropathy KW - enteropathy KW - peptide KW - experimental autoimmune neuritis Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115239 VL - 9 IS - 10 ER - TY - JOUR A1 - Beyer, Felix A1 - Jadasz, Janusz A1 - Samper Agrelo, Iria A1 - Schira‐Heinen, Jessica A1 - Groh, Janos A1 - Manousi, Anastasia A1 - Bütermann, Christine A1 - Estrada, Veronica A1 - Reiche, Laura A1 - Cantone, Martina A1 - Vera, Julio A1 - Viganò, Francesca A1 - Dimou, Leda A1 - Müller, Hans Werner A1 - Hartung, Hans‐Peter A1 - Küry, Patrick T1 - Heterogeneous fate choice of genetically modulated adult neural stem cells in gray and white matter of the central nervous system JF - Glia N2 - Apart from dedicated oligodendroglial progenitor cells, adult neural stem cells (aNSCs) can also give rise to new oligodendrocytes in the adult central nervous system (CNS). This process mainly confers myelinating glial cell replacement in pathological situations and can hence contribute to glial heterogeneity. Our previous studies demonstrated that the p57kip2 gene encodes an intrinsic regulator of glial fate acquisition and we here investigated to what degree its modulation can affect stem cell‐dependent oligodendrogenesis in different CNS environments. We therefore transplanted p57kip2 knockdown aNSCs into white and gray matter (WM and GM) regions of the mouse brain, into uninjured spinal cords as well as in the vicinity of spinal cord injuries and evaluated integration and differentiation in vivo. Our experiments revealed that under healthy conditions intrinsic suppression of p57kip2 as well as WM localization promote differentiation toward myelinating oligodendrocytes at the expense of astrocyte generation. Moreover, p57kip2 knockdown conferred a strong benefit on cell survival augmenting net oligodendrocyte generation. In the vicinity of hemisectioned spinal cords, the gene knockdown led to a similar induction of oligodendroglial features; however, newly generated oligodendrocytes appeared to suffer more from the hostile environment. This study contributes to our understanding of mechanisms of adult oligodendrogenesis and glial heterogeneity and further reveals critical factors when considering aNSC mediated cell replacement in injury and disease. KW - glial fate modulation KW - myelin KW - neural stem cell KW - p57kip2 KW - regional heterogeneity KW - spinal cord injury KW - transplantation Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218566 VL - 68 IS - 2 SP - 393 EP - 406 ER - TY - JOUR A1 - Merkies, Ingemar S.J. A1 - van Schaik, Ivo N. A1 - Léger, Jean-Marc A1 - Bril, Vera A1 - van Geloven, Nan A1 - Hartung, Hans-Peter A1 - Lewis, Richard A. A1 - Sobue, Gen A1 - Lawo, John-Philip A1 - Durn, Billie L. A1 - Cornblath, David R. A1 - De Bleecker, Jan L. A1 - Sommer, Claudia A1 - Robberecht, Wim A1 - Saarela, Mika A1 - Kamienowski, Jerzy A1 - Stelmasiak, Zbigniew A1 - Tackenberg, Björn A1 - Mielke, Orell T1 - Efficacy and safety of IVIG in CIDP: Combined data of the PRIMA and PATH studies JF - Journal of the Peripheral Nervous System N2 - Intravenous immunoglobulin (IVIG) is a potential therapy for chronic inflammatory demyelinating polyneuropathy (CIDP). To investigate the efficacy and safety of the IVIG IgPro10 (Privigen) for treatment of CIDP, results from Privigen Impact on Mobility and Autonomy (PRIMA), a prospective, open-label, single-arm study of IVIG in immunoglobulin (Ig)-naïve or IVIG pre-treated subjects (NCT01184846, n = 28) and Polyneuropathy And Treatment with Hizentra (PATH), a double-blind, randomized study including an open-label, single-arm IVIG phase in IVIG pre-treated subjects (NCT01545076, IVIG restabilization phase n = 207) were analyzed separately and together (n = 235). Efficacy assessments included change in adjusted inflammatory neuropathy cause and treatment (INCAT) score, grip strength and Medical Research Council (MRC) sum score. Adverse drug reactions (ADRs) and ADRs/infusion were recorded. Adjusted INCAT response rate was 60.7% in all PRIMA subjects at Week 25 (76.9% in IVIG pre-treated subjects) and 72.9% in PATH. In the pooled cohort (n = 235), INCAT response rate was 71.5%; median time to INCAT improvement was 4.3 weeks. No clear demographic differences were noticed between early (responding before Week 7, n = 148) and late responders (n = 21). In the pooled cohort, median change from baseline to last observation was −1.0 (interquartile range −2.0; 0.0) point for INCAT score; +8.0 (0.0; 20.0) kPa for maximum grip strength; +3.0 (1.0; 7.0) points for MRC sum score. In the pooled cohort, 271 ADRs were reported in 105 subjects (44.7%), a rate of 0.144 ADRs per infusion. This analysis confirms the efficacy and safety of IgPro10, a recently FDA-approved IVIG for CIDP, in a population of mainly pre-treated subjects with CIDP [Correction added on 14 March 2019 after first online publication: the INCAT response rate has been corrected.]. KW - CIDP KW - efficacy KW - IVIG KW - PATH KW - PRIMA Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224013 VL - 24 ER -