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Inflammation and related oxidative stress have been proposed as central mediators of cortical damage, yet meningeal and cortical inflammation is not specific to MS, but also occurs in other diseases. The first aim of this study was to test whether cortical demyelination was specific for demyelinating CNS diseases compared to other CNS disorders with prominent meningeal and cortical inflammation. The second aim was to assess whether oxidative tissue damage was associated with the extent of neuroaxonal damage. We studied a large cohort of patients diagnosed with demyelinating CNS diseases and non\u2010demyelinating diseases of autoimmune, infectious, neoplastic or metabolic origin affecting the meninges and the cortex. Included were patients with MS, acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), viral and bacterial meningoencephalitis, progressive multifocal leukoencephalopathy (PML), subacute sclerosing panencephalitis (SSPE), carcinomatous and lymphomatous meningitis and metabolic disorders such as extrapontine myelinolysis, thus encompassing a wide range of adaptive and innate cytokine signatures. Using myelin protein immunohistochemistry, we found cortical demyelination in MS, ADEM, PML and extrapontine myelinolysis, whereby each condition showed a disease\u2010specific histopathological pattern. Remarkably, extensive ribbon\u2010like subpial demyelination was only observed in MS, thus providing an important pathogenetic and diagnostic cue. Cortical oxidative injury was detected in both demyelinating and non\u2010demyelinating CNS disorders. Our data demonstrate that meningeal and cortical inflammation alone accompanied by oxidative stress are not sufficient to generate the extensive subpial cortical demyelination found in MS, but require other MS\u2010specific factors.<\/jats:p>","DOI":"10.1111\/bpa.12813","type":"journal-article","created":{"date-parts":[[2020,1,9]],"date-time":"2020-01-09T02:07:41Z","timestamp":1578535661000},"page":"641-652","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Extensive subpial cortical demyelination is specific to multiple sclerosis"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8063-9765","authenticated-orcid":false,"given":"Andreas","family":"Junker","sequence":"first","affiliation":[{"name":"Institute of Neuropathology University Medical Center G\u00f6ttingen Georg August University G\u00f6ttingen Robert\u2010Koch\u2010Str. 40 37075 G\u00f6ttingen Germany"},{"name":"Department 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