Extensive subpial cortical demyelination is specific to multiple sclerosis. Junker A, Wozniak J, Voigt D, Scheidt U, Antel J, Wegner C, Brück W, Stadelmann C. Brain Pathol. 2020. doi: 10.1111/bpa.12813. [Epub ahead of print]
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.
Cortical demyelination is loss of myelin around the outside of the brain. This has been associated with cognitive problems. When I was a young researcher, MS was a white matter disease.
This is because the imagers and pathologists had forgotten the original work done more than a hundred years ago and notably because the imagers could not image the grey matter (place where the nerve heads sit) with their MRI machines and could only see the white matter the bit where the axon (nerve bodies) are found.
The pathologists were too lazy to do their own work, as it was their technicians preparing the brains that could surely see the grey matter lesions with their eyes (you often don’t need a microscope), the pathologists then told the technicians there was no myelin in the grey matter so they destained their sections until their was no staining in the grey matter and the cortial lesions were missed by the pathologists and then staining came along and even they couldn’t miss it at that point.
In this study they looked at different diseases and they can find cortical demyelination but not the large ribbons of myelin loss found in MS (see image). So that suggests that there is something different happening in MS. What is it?. I don’t know?
Could it be something in the spinal fluid that surrounds the brain, it seems a good candidate. Anyway this could help geting a more definative diagnosis at post-postem….However, the cynic in me now says if this is true.
I used to believe what pathologists said without question, but now the first thing I think is, we have to see this repeated by another unrelated lab. Why?
This is because far too often pathologists do not see and say the same thing, even on fundemental aspects. What do I mean? Recently I have seen human remyelination questioned by the animal people (probably in response to a group saying that human repair is different from animal remyelination based on analysis of a shadow plaque) and frankly the response of a senior pathologists to counter what a shadow palque is, was pretty weak. Then we have the different types of lesions that make up MS and others don’t see them. To top it all , recently I saw two other senior people present completely different ideas based on doing the same pathology. Their talks were one after the other, within 10 minutes of each other, and neither questioned the other.