When we used to go to meetings it would often be the case that Pathologist would have a go at the animal modelers where they would say that animal models did not look like MS. I had to agree with them, but it was typical to get this response over and over again. Never would a scientist get up and say the trial didnt work because you messed it up. Likewise the pathologists would never be questioned and often they would not even question themselves when they showed differences. However it has started. With the suggestion that humans remyelinate differently to rodents, the remyelinators started to question the pathologists to say the shadow plaques were not remyelination and so when these were used to say rodent studies were wrong they were not looking at remyelination. I remember this being asked of a very senior pathologists and their response was not great to say the least. Any way the human and the rodent remyelinators puckered up and now say both are correct. Anyway I digress
We you go to a murder scene you have the dead body, you may have the muder weapon and you may even have the place where the murder took place but seldom so you have the perp who did it. They are off as quick as you can say get Columbo…yep showing some age….OK get Luther. Any way when we get pathology we often get the story as if the murder is still there. We have the dying oligodendrocytes and not a lymphocyte in sight and so it must be something else killing the oligodendrocyte. This may be so but maybe the lymphocyte has an invisible death ray gun or maybe they have left some cellular novichok on a nerve or sent out a poison gas to do the dastardly deal.
In MS for years focus was on the white matter (nerve bodies with myelin) verses the grey matter (nerve heads) as the MRI scanners could not see the grey matter lesions. These occur along the brain surface like a ribbon. But when you look in the grey matter there are very few cells to be found, so you make up an idea that it is a unknown factor. However, is the murderer else where? The answer based on this study says yes it is. The damage occurs in the white matter at the lesion in the grey matter shows damage and shrinks. The connectome project has been mapping the nerve tracts to see where they start and where they lead to. If you find white matter lesions you can then map them back to where the the nerve fibres go in the grey matter. Doing this they can find that areas of grey matter loss and these relate to white matter damage
Bussas M, Grahl S, Pongratz V, Berthele A, Gasperi C, Andlauer T, Gaser C, Kirschke JS, Wiestler B, Zimmer C, Hemmer B, Mühlau M. Gray matter atrophy in relapsing-remitting multiple sclerosis is associated with white matter lesions in connecting fibers. Mult Scler. 2021 Sep 30:13524585211044957
Background: Lesions of brain white matter (WM) and atrophy of brain gray matter (GM) are well-established surrogate parameters in multiple sclerosis (MS), but it is unclear how closely these parameters relate to each other.
Objective: To assess across the whole cerebrum whether GM atrophy can be explained by lesions in connecting WM tracts.
Methods: GM images of 600 patients with relapsing-remitting MS (women = 68%; median age = 33.0 years, median expanded disability status scale score = 1.5) were converted to atrophy maps by data from a healthy control cohort. An atlas of WM tracts from the Human Connectome Project and individual lesion maps were merged to identify potentially disconnected GM regions, leading to individual disconnectome maps. Across the whole cerebrum, GM atrophy and potentially disconnected GM were tested for association both cross-sectionally and longitudinally.
Results: We found highly significant correlations between disconnection and atrophy across most of the cerebrum. Longitudinal analysis demonstrated a close temporal relation of WM lesion formation and GM atrophy in connecting fibers.
Conclusion: GM atrophy is associated with WM lesions in connecting fibers. Caution is warranted when interpreting group differences in GM atrophy exclusively as differences in early neurodegeneration independent of WM lesion formation.
General Disclaimer: Please note that the opinions expressed here are those of the author and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust and are not meant to be interpreted as personal clinical advice.