Kortikale Demyelinisierung bei entzündlichen, neoplastischen und metabolischen ZNS-Erkrankungen
Cortical demyelination in inflammatory, neoplastic and metabolic CNS deseases
von Jadwiga Zyta Wozniak
Datum der mündl. Prüfung:2018-11-27
Erschienen:2018-11-06
Betreuer:Prof. Dr. Wolfgang Brück
Gutachter:Prof. Dr. Martin Oppermann
Gutachter:Prof. Dr. Jutta Gärtner
Dateien
Name:FINAL Dissertation Jadwiga Wozniak.pdf
Size:2.85Mb
Format:PDF
Zusammenfassung
Englisch
Cortical demyelinated lesions are frequent and widespread in chronic multiple sclerosis (MS) patients, and may contribute to disease progression. Cortical and subpial lesions were found in early MS stages indicating that they may be an inherent and early feature of the disease process. Moreover, inflammation-associated genes were shown to be upregulated in early cortical lesions. Yet, the precise mechanisms leading to the formation of subpial cortical demyelination remain elusive. To test whether cortical demyelination and especially subpial demyelination occurs in diseases other than MS, we studied a large cohort of patients pathologically diagnosed with diseases of autoimmune, infectious, neoplastic or metabolic origin affecting the cortex. Included were, among others, patients with MS, acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), acute and chronic viral and bacterial meningoencephalitis, progressive multifocal leukoencephathy (PML), subacute sclerosing panencephalitis (SSPE), meningeal carcinomatosis, lymphomatous meningitis, and metabolic disorders such as extrapontine myelinolysis, thus encompassing a wide range of adaptive and innate cytokine signatures. Using immunohistochemistry for myelin basic protein (MBP), proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG) we found cortical demyelination besides MS in ADEM, PML and extrapontine myelinolysis. Importantly, each of these diseases had a disease specific cortical demyelination pattern and bandlike extensive subpial demyelination was only found in MS. In particular subpial demyelination occurred also in PML but in contrast to MS lesions had a small focal character. These study data extend and confirm previous findings and suggest that extensive bandlike subpial demyelination is specific for MS, thus providing an important diagnostic cue. Obviously, disease-specific milieus or heterogeneous triggers are necessary causing demyelination such as specific cytokines, chemokines and genetic background. Further molecular studies are required to dissect the specific mechanisms of demyelination in MS and other demyelinating diseases.
Keywords: MS; ADEM; NMO; PML; demyelination; syphilis; TBC; extrapontine myelinolysis; SSPE