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Brain Pathol. 2020 Jan 8. doi: 10.1111/bpa.12813. [Epub ahead of print]

Extensive subpial cortical demyelination is specific to multiple sclerosis.

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Institute of Neuropathology, University Medical Center Göttingen, Georg August University Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany.
Department of Neuropathology, University Hospital Essen, Hufelandstr. 55, 45147, Essen, Germany.
Montreal Neurological Institute, McGill University Health Centre, 2155 Guy Street, Montreal, Canada.
Department of Child and Adolescent Psychiatry/Psychotherapy, University Medical Center Göttingen, Georg August University Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany.


Cortical demyelinated lesions are frequent and widespread in chronic multiple sclerosis (MS) patients, and may contribute to disease progression. 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-demyelinating 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-specific histopathological pattern. Remarkably, extensive ribbon-like 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-demyelinating 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-specific factors.


Multiple sclerosis (MS); acute disseminated encephalomyelitis (ADEM); carcinomatous and lymphomatous meningitis; cortical demyelination; meningitis; neuromyelitis optica (NMO); oxidative stress; progressive multifocal leukoencephalopathy (PML); subpial lesions


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