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Apheresis therapy in immunopathologically classified multiple sclerosis patients

dc.contributor.advisorMetz, Imke PD Dr.
dc.contributor.authorStork, Lidia
dc.date.accessioned2020-01-31T10:21:54Z
dc.date.available2020-02-12T23:50:03Z
dc.date.issued2020-01-31
dc.identifier.urihttp://hdl.handle.net/21.11130/00-1735-0000-0005-1303-2
dc.identifier.urihttp://dx.doi.org/10.53846/goediss-7829
dc.language.isoengde
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc610de
dc.titleApheresis therapy in immunopathologically classified multiple sclerosis patientsde
dc.typecumulativeThesisde
dc.contributor.refereeMetz, Imke PD Dr.
dc.date.examination2020-02-05
dc.description.abstractengPlasma exchange and immunoadsorption are second-line apheresis therapies for steroid-unresponsive multiple sclerosis relapses with a variable response rate. The mechanism of action of these therapies is assumed to be the removal of disease-causing agents such as antibodies, immune complexes and cytokines. A retrospective analysis of different demographical, clinical and histological parameters, which potentially could predict responses to apheresis therapies, was performed in 69 patients with multiple sclerosis lesions classified into pathological patterns I-III. The primary therapy outcome parameter was a functionally relevant improvement of the relapse-related neurological deficit. Radiological and expanded disability status scale changes were secondary outcome parameters. We found that immunopathological patterns I and II, as well as application of immunoadsorption and involvement of the cognitive function with the relapse were positive predictive factors for a functional therapy response. In contrast, immunopathological pattern III and brainstem involvement with the relapse were negative predictive factors. A functional therapy response was observed in 31% (5/16) of pattern I and 55% (22/40) of pattern II patients, whereas no improvement was found in pattern III patients (0/13, p<0.001 pattern II versus III). Radiological findings supported the primary outcome. Lesion improvements were found in 25%, 56% and 11% of patterns I, II and III, respectively. The expanded disability status scale response rates again showed highest success rates in pattern II patients (40%) and were 25% and 0% for patients with patterns I and III. Our results show that the response to apheresis treatment could be predicted by immunopathological patterns as well as involvement of the cognitive and brainstem systems. Potentially, IA is more effective than PLEX, but this has to be clarified in further studies. Different pathological subtypes of early active multiple sclerosis lesions suggests different pathophysiological mechanism of lesion development and thus may explain the varying therapy responses. Pattern I and II lesions show sharp lesion edges and an infiltration with T-cells and macrophages. Additionally, an antibody and complement-mediated mechanism of demyelination is suggested in pattern II. These patients also showed the most success from the apheresis treatment. In contrast, in pattern III lesions a primary oligodendrocytic damage may play an important role in lesion pathogenesis; patients showing this pattern are not amenable to apheresis treatments.de
dc.contributor.coRefereeKoziolek, Michael Prof. Dr.
dc.contributor.thirdRefereeHuppke, Peter Prof. Dr.
dc.subject.enginflammatory demyelinationde
dc.subject.engApheresis therapyde
dc.subject.engmultiple sclerosisde
dc.subject.engimmunopatternde
dc.identifier.urnurn:nbn:de:gbv:7-21.11130/00-1735-0000-0005-1303-2-6
dc.affiliation.instituteMedizinische Fakultätde
dc.subject.gokfullMedizin (PPN619874732)de
dc.subject.gokfullNeurologie - Allgemein- und Gesamtdarstellungen (PPN619876247)de
dc.subject.gokfullPathologie / Pathologische Anatomie / Histopathologie / Zytopathologie - Allgemein- und Gesamtdarstellungen (PPN619875674)de
dc.description.embargoed2020-02-12
dc.identifier.ppn1689056126


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