Diem, Ricarda

[["dc.bibliographiccitation.firstpage","81"],["dc.bibliographiccitation.journal","Annals of Neurology"],["dc.bibliographiccitation.lastpage","93"],["dc.bibliographiccitation.volume","66"],["dc.contributor.author","Gadjanski, Ivana"],["dc.contributor.author","Boretius, Susann"],["dc.contributor.author","Williams, Sarah K."],["dc.contributor.author","Lingor, Paul"],["dc.contributor.author","Knöferle, Johanna"],["dc.contributor.author","Sättler, Muriel B."],["dc.contributor.author","Fairless, Richard"],["dc.contributor.author","Hochmeister, Sonja"],["dc.contributor.author","Sühs, Kurt-Wolfram"],["dc.contributor.author","Michaelis, Thomas"],["dc.contributor.author","Frahm, Jens"],["dc.contributor.author","Storch, Maria K."],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Diem, Ricarda"],["dc.date.accessioned","2019-07-09T11:52:52Z"],["dc.date.available","2019-07-09T11:52:52Z"],["dc.date.issued","2009"],["dc.description.abstract","Objective: The aim of this study was to investigate the role of voltage-dependent calcium channels (VDCCs) in axon degeneration during autoimmune optic neuritis. Methods: Calcium ion (Ca2 ) influx into the optic nerve (ON) through VDCCs was investigated in a rat model of optic neuritis using manganese-enhanced magnetic resonance imaging and in vivo calcium imaging. After having identified the most relevant channel subtype (N-type VDCCs), we correlated immunohistochemistry of channel expression with ON histopathology. In the confirmatory part of this work, we performed a treatment study using -conotoxin GVIA, an N-type specific blocker. Results: We observed that pathological Ca2 influx into ONs during optic neuritis is mediated via N-type VDCCs. By analyzing the expression of VDCCs in the inflamed ONs, we detected an upregulation of 1B, the pore-forming subunit of N-type VDCCs, in demyelinated axons. However, high expression levels were also found on macrophages/activated microglia, and lower levels were detected on astrocytes. The relevance of N-type VDCCs for inflammation-induced axonal degeneration and the severity of optic neuritis was corroborated by treatment with -conotoxin GVIA. This blocker led to decreased axon and myelin degeneration in the ONs together with a reduced number of macrophages/activated microglia. These protective effects were confirmed by analyzing the spinal cords of the same animals. Interpretation: We conclude that N-type VDCCs play an important role in inflammation-induced axon degeneration via two mechanisms: First, they directly mediate toxic Ca2 influx into the axons; and second, they contribute to macrophage/microglia function, thereby promoting secondary axonal damage."],["dc.identifier.doi","10.1002/ ana.21668"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6088"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60296"],["dc.language.iso","en"],["dc.subject.ddc","610"],["dc.title","Role of N-Type Voltage-Dependent Calcium Channels in Autoimmune Optic Neuritis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e010956"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","BMJ Open"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Diem, Ricarda"],["dc.contributor.author","Molnar, Fanni"],["dc.contributor.author","Beisse, Flemming"],["dc.contributor.author","Gross, Nikolai"],["dc.contributor.author","Drueschler, Katharina"],["dc.contributor.author","Heinrich, Sven P."],["dc.contributor.author","Joachimsen, Lutz"],["dc.contributor.author","Rauer, Sebastian"],["dc.contributor.author","Pielen, Amelie"],["dc.contributor.author","Suehs, Kurt-Wolfram"],["dc.contributor.author","Linker, Ralf Andreas"],["dc.contributor.author","Huchzermeyer, Cord"],["dc.contributor.author","Albrecht, Philipp"],["dc.contributor.author","Hassenstein, Andrea"],["dc.contributor.author","Aktas, Orhan"],["dc.contributor.author","Guthoff, Tanja"],["dc.contributor.author","Tonagel, Felix"],["dc.contributor.author","Kernstock, Christoph"],["dc.contributor.author","Hartmann, Kathrin"],["dc.contributor.author","Kuempfel, Tania"],["dc.contributor.author","Hein, Katharina"],["dc.contributor.author","van Oterendorp, Christian"],["dc.contributor.author","Grotejohann, Birgit"],["dc.contributor.author","Ihorst, Gabriele"],["dc.contributor.author","Maurer, Julia"],["dc.contributor.author","Mueller, Matthias"],["dc.contributor.author","Volkmann, Martin"],["dc.contributor.author","Wildemann, Brigitte"],["dc.contributor.author","Platten, Michael"],["dc.contributor.author","Wick, Wolfgang"],["dc.contributor.author","Heesen, Christoph"],["dc.contributor.author","Schiefer, Ulrich"],["dc.contributor.author","Wolf, Sebastian"],["dc.contributor.author","Lagreze, Wolf A."],["dc.date.accessioned","2018-11-07T10:20:35Z"],["dc.date.available","2018-11-07T10:20:35Z"],["dc.date.issued","2016"],["dc.description.abstract","Introduction Optic neuritis leads to degeneration of retinal ganglion cells whose axons form the optic nerve. The standard treatment is a methylprednisolone pulse therapy. This treatment slightly shortens the time of recovery but does not prevent neurodegeneration and persistent visual impairment. In a phase II trial performed in preparation of this study, we have shown that erythropoietin protects global retinal nerve fibre layer thickness (RNFLT-G) in acute optic neuritis; however, the preparatory trial was not powered to show effects on visual function. Methods and analysis Treatment of Optic Neuritis with Erythropoietin (TONE) is a national, randomised, double-blind, placebo-controlled, multicentre trial with two parallel arms. The primary objective is to determine the efficacy of erythropoietin compared to placebo given add-on to methylprednisolone as assessed by measurements of RNFLT-G and low-contrast visual acuity in the affected eye 6months after randomisation. Inclusion criteria are a first episode of optic neuritis with decreased visual acuity to 0.5 (decimal system) and an onset of symptoms within 10days prior to inclusion. The most important exclusion criteria are history of optic neuritis or multiple sclerosis or any ocular disease (affected or non-affected eye), significant hyperopia, myopia or astigmatism, elevated blood pressure, thrombotic events or malignancy. After randomisation, patients either receive 33000 international units human recombinant erythropoietin intravenously for 3 consecutive days or placebo (0.9% saline) administered intravenously. With an estimated power of 80%, the calculated sample size is 100 patients. The trial started in September 2014 with a planned recruitment period of 30months. Ethics and dissemination TONE has been approved by the Central Ethics Commission in Freiburg (194/14) and the German Federal Institute for Drugs and Medical Devices (61-3910-4039831). It complies with the Declaration of Helsinki, local laws and ICH-GCP. Trial registration number NCT01962571."],["dc.identifier.doi","10.1136/bmjopen-2015-010956"],["dc.identifier.isi","000374052300146"],["dc.identifier.pmid","26932144"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13259"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41917"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Bmj Publishing Group"],["dc.relation.issn","2044-6055"],["dc.rights","CC BY-NC 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/4.0"],["dc.title","Treatment of optic neuritis with erythropoietin (TONE): a randomised, double-blind, placebo-controlled trialstudy protocol"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e0162583"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Obert, D."],["dc.contributor.author","Helms, G."],["dc.contributor.author","Sättler, M. B."],["dc.contributor.author","Jung, K."],["dc.contributor.author","Kretzschmar, B."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Dechent, P."],["dc.contributor.author","Diem, R."],["dc.contributor.author","Hein, K."],["dc.date.accessioned","2017-09-07T11:44:38Z"],["dc.date.available","2017-09-07T11:44:38Z"],["dc.date.issued","2016"],["dc.description.abstract","Magnetic resonance spectroscopy (MRS) provides the unique ability to monitor several disease-related pathological processes via their characteristic metabolic markers in vivo. In the present study metabolic compositions were assessed every six months over the period of two years in 36 patients with Multiple Sclerosis (MS) including 21 relapsing-remitting (RR), 15 secondary progressive (SP) patients and 12 normal subjects. The concentrations of the main MRS-detectable metabolites N-acetylaspartate and N-acetylaspartylglutamate (tNAA), creatine and phosphocreatine (tCr), choline containing compounds (Cho), myo-Inositol (Ins), glutamine and glutamate (Glx) and their ratios were calculated in the normal appearing white matter (NAWM) and in selected non-enhancing white matter (WM) lesions. Association between metabolic concentrations in the NAWM and disability were investigated. Concentration of tNAA, a marker for neuroaxonal integrity, did not show any difference between the investigated groups. However, the patients with SPMS showed significant reduction of tNAA in the NAWM over the investigation period of two years indicating diffuse neuroaxonal loss during the disease course. Furthermore, we found a significant increase of Ins, Ins/tCr and Ins/tNAA in WM lesions independently from the course of the disease suggesting ongoing astrogliosis in silent-appearing WM lesions. Analyzing correlations between MRS metabolites in the NAWM and patients clinical status we found the positive correlation of Ins/tNAA with disability in patients with RRMS. In SPMS positive correlation of Cho with disability was found."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2016"],["dc.format.extent","15"],["dc.identifier.doi","10.1371/journal.pone.0162583"],["dc.identifier.gro","3141620"],["dc.identifier.isi","000383723700009"],["dc.identifier.pmid","27636543"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13693"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2011"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Bayer Vital GmbH, Leverkusen, Germany; Merck Serono GmbH, Darmstadt"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Brain Metabolite Changes in Patients with Relapsing-Remitting and Secondary Progressive Multiple Sclerosis: A Two-Year Follow-Up Study"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1666"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","17"],["dc.contributor.author","Sühs, Kurt-Wolfram"],["dc.contributor.author","Papanagiotou, Panagiotis"],["dc.contributor.author","Hein, Katharina"],["dc.contributor.author","Pul, Refik"],["dc.contributor.author","Scholz, Kerstin"],["dc.contributor.author","Heesen, Christoph"],["dc.contributor.author","Diem, Ricarda"],["dc.date.accessioned","2019-07-09T11:42:55Z"],["dc.date.available","2019-07-09T11:42:55Z"],["dc.date.issued","2016"],["dc.description.abstract","Changes in cerebral lesion load by magnetic resonance imaging (MRI) in patients from a double-blind, placebo-controlled, phase II study on erythropoietin in clinically isolated optic neuritis (ClinicalTrials.gov, NCT00355095) were analyzed. Therefore, patients with acute optic neuritis were assigned to receive either 33,000 IU of recombinant human erythropoietin (IV) daily for three days, or a placebo, as an add-on to methylprednisolone. Of 35 patients, we investigated changes in cerebral lesion load in MRIs obtained at baseline and at weeks 4, 8, and 16. In 5 of the 35 patients, we found conversion into multiple sclerosis (MS) based on MRI progression only. These five patients had received the placebo. Another five patients showed MRI progression together with relapses. Three of these patients had received erythropoietin, and two the placebo. Yet, analyzing the change in absolute numbers of periventricular, juxtacortical, and infratentorial lesions including gadolinium-enhancing lesions, there were no significant differences between the groups. Although effective in terms of retinal nerve fiber layer protection, erythropoietin treatment of acute isolated optic neuritis did not influence further evolution of MRI lesions in the brain when comparing absolute numbers. However, early conversion from clinically isolated syndrome to MS assessed by MRI activity seemed to occur more frequently in the placebo-treated group."],["dc.identifier.doi","10.3390/ijms17101666"],["dc.identifier.pmid","27706045"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13993"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58784"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1422-0067"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Disease Activity and Conversion into Multiple Sclerosis after Optic Neuritis Is Treated with Erythropoietin"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e51645"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Suehs, Kurt-Wolfram"],["dc.contributor.author","Hein, Katharina"],["dc.contributor.author","Pehlke, Jens R."],["dc.contributor.author","Kaesmann-Kellner, Barbara"],["dc.contributor.author","Diem, Ricarda"],["dc.date.accessioned","2018-11-07T09:02:19Z"],["dc.date.available","2018-11-07T09:02:19Z"],["dc.date.issued","2012"],["dc.description.abstract","Background: Optic neuritis is associated with neurodegeneration leading to chronic impairment of visual functions. Objective: This study investigated whether early treatment with interferon beta (IFN-beta) slows retinal nerve fibre layer (RNFL) thinning in clinically isolated optic neuritis. Methods: Twenty patients with optic neuritis and visual acuity decreased to <= 0.5 (decimal system) were included into this prospective, open-label, parallel group 4-month observation. After methylprednisolone pulse therapy, 10 patients received IFN-beta from week 2 onwards. This group was compared to 10 patients free of any disease modifying treatment (DMT). The parameter of interest was change in RNFL thickness assessed at baseline and at weeks 4, 8, and 16. Changes in visual acuity, visual field, and visual evoked potentials (VEPs) served as additional outcome parameters. Results: RNFL thinning did not differ between the groups with a mean reduction of 9.80 +/- 2.80 mu m in IFN-beta-treated patients (+/- SD) vs. 12.44 +/- 5.79 mu m in patients who did not receive DMT (baseline non-affected eye minus affected eye at week 16; p = 0.67, t-test, 95% confidence interval: -15.77 to 10.48). Parameters of visual function did not show any differences between the groups either. Conclusions: In isolated optic neuritis, early IFN-beta treatment did not influence RNFL thinning nor had it any effect on recovery of visual functions. Citation: Suhs K-W, Hein K, Pehlke JR, Kasmann-Kellner B, Diem R (2012) Retinal Nerve Fibre Layer Thinning in Patients with Clinically Isolated Optic Neuritis and Early Treatment with Interferon-Beta. PLoS ONE 7(12): e51645. doi:10.1371/journal.pone.0051645"],["dc.description.sponsorship","Bayer Healthcare, Leverkusen, Germany; Merck Serono GmbH, Darmstadt"],["dc.identifier.doi","10.1371/journal.pone.0051645"],["dc.identifier.isi","000312386600032"],["dc.identifier.pmid","23272128"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8450"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24653"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","Retinal Nerve Fibre Layer Thinning in Patients with Clinically Isolated Optic Neuritis and Early Treatment with Interferon-Beta"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]