Pathologists should play more cluedo:-)


Cluedo is a game where someone gets killed and you have to work out who is the perp, the weapon and the place where the attack took place. Pathology is like murder case (Hopefully this will launch when we were on blogger this word triggered the post to become for 18 year olds) and you are left with the crime scene. You have to work out who dunnit.

Cluedo | Nintendo Switch download software | Games | Nintendo

So you find John Doe in a pristine bedroom. What do you conclude? You say the person died of a heart attack or maybe they killed themselves if you find a pot of pills open, as you don’t do more investigation.

This is the “real MS” a dying oligodendrocyte without a lymphocyte in sight

Maybe some investigators could deduce it wasn’t the pills, based on their knowledge and experience

World Collectors Net – Cluedo Detecting the Value of this Classic Game

However Mrs Chalky White was making a peanut and jelly sandwich in the kitchen and she dropped the jammy sandwich into the central air ducting and once John got a whiff of the peanut butter they has an anaphylactic response, as he had a nut allergy, and it was too late for the pills to work and his epipen (adrenaline/epherine) in the fridge had expired years ago.

Yep I am playing Devil’s advocate but this idea of grey matter lesions (Joe Doe) in the brain (bedroom) being caused by white blood cells (Chalky White) entering the spinal cord (kitchen) to damage axons (air ducting) is just as plausible as the oligodendrocyte apoptosis without any effect of the immune system (Real MS) due to some unknown triggers.

Now if you play more Cluedo you may be used to speculating abit more.

But in this study they looked through a load of pathology papers on grey matter lesions and they concluded that they were often associated with white matter lesions and suggested that the effect in the grey matter may be secondary to effects in the white matter. So the white matter is full of axons where the nerve body lives and the grey matter is where the nerve heads live. If you chop the body in two would it be surprising that the head dies. It is just how you look at things.

It was easier to see this relaionship early and some may argue that different. However, it is probably easier to see things earlier, just like it is easier to work out what a potent DMT is doing compared to a weak DMT, because what ever it is doing it is not doing as well as a highly active DMT

Lie IA, Weeda MM, Mattiesing RM, Mol MAE, Pouwels PJW, Barkhof F, Torkildsen Ø, Bø L, Myhr KM, Vrenken H. Relationship Between White Matter Lesions and Gray Matter Atrophy in Multiple Sclerosis: A Systematic Review. Neurology. 2022 Feb 16:10.1212/WNL.0000000000200006. 

Background: There is currently no consensus about the extent of gray matter (GM) atrophy that can be attributed to secondary changes following white matter (WM) lesions, or the temporal and spatial relationships between the two phenomena. Elucidating this interplay will broaden the understanding of the combined inflammatory and neurodegenerative pathophysiology of multiple sclerosis (MS), and separating atrophic changes due to primary and secondary neurodegenerative mechanisms will then be pivotal to properly evaluate treatment effects, especially if these treatments target the different processes individually.

Objective: To untangle these complex pathological mechanisms, this systematic review provides an essential first step: an objective and comprehensive overview of the existing in vivo knowledge of the relationship between brain WM lesions and GM atrophy, in patients diagnosed with MS. The overall aim was to clarify the extent to which WM lesions associate with both global and regional GM atrophy, and how this may differ in the different disease subtypes.

Methods: We searched MEDLINE (through PubMed) and Embase for reports containing direct associations between brain GM and WM lesion measures obtained by conventional MRI sequences in patients with clinically isolated syndrome (CIS) and MS. No restriction was applied for publication date. The quality and risk of bias in included studies was evaluated using the Quality Assessment Tool for observational cohort and cross-sectional studies (NIH, Bethesda, MA). Qualitative and descriptive analyses were performed.

Results: A total of 90 articles were included. WM lesion volumes were mostly related to global, cortical and deep GM volumes, and those significant associations were almost without exception negative, indicating that higher WM lesion volumes were associated with lower GM volumes or lower cortical thicknesses. The most consistent relation between WM lesions and GM atrophy was seen in early (relapsing) disease, and less so in progressive MS.

Conclusion: The findings suggest that GM neurodegeneration is mostly secondary to damage in the WM during early disease stages, while becoming more detached and dominated by other, possibly primary neurodegenerative disease mechanisms, in progressive MS.

Disclaimer this is the view of the author and not an Instituion

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  • I share your deep love for pathologists ;). The problem lies in the discipline: a pathologist’s nature is to rely on direct evidence with specimens. White blood cells actually crossing the BBB or slowing of nerve conduction from central damage are too amorphous for them. ( I note, A real but little discussed problem pwms encounter are ophthalmologist/ pathologists are permitted to practice neuro-ophthalmology with little training in diagnosing visual phenomena caused by MS. As a result, many pwms with visual symptoms often get told they suffer from dry eyes, anxiety, malingering, or plain crazy. Ophthalmology Boards need to step up require a minimum level of training for those who practice neuro-ophthalmology. Just saying. )

  • “If you chop the body in two would it be surprising that the head dies”…….graphic, yet effective way to describe the mechanisms of this nasty disease.

    This study is a bit complex for me to fully understand. However, I do appreciate their initiative to try and determine the usefulness of certain diagnostic factors being used to classify the “stages” of MS.

    It just seems like any time I read a study based on a “meta-analysis”, the authors tend to find more correlations than causations. (Which can be done with any large data set)

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