Education: MS Lesion Types

We have been talking about pathology of MS recently. There has been much made of the types of lesions reported by John Prineas of a post-mortem taken after the unusual case of a lethal relapse that showed oligodendrocyte damage in the absence of white blood cells, This has been used my some to question the autoimmune element of MS. 

However, as we have also seen that you do not need to have white blood cells around if the damage is triggered by antibodies that can stimulate the microglia to do their worse. 

Now the problem with understanding pathology in MS, is that it sadly occurs after the death. Therefore you only see a snap shoot in time and it is impossible to know what has come before and what may of occurred later. However, in cases where the lesions have looked like tumors then  biopsies have been taken and when the biospies were looked at under the microscope, it has been proposed that there are 4 different types of white matter lesion.

Pattern I (~15% Lesions)
-Centered around venule (vein) with sharp, demarcated edges
-T-cell/macrophage associated
-extensive remyelination
-oliogodendrocytes in lesion centre

Pattern II (~58% lesions)
-Antibody/complement associated, lesions contain large quantities of immunoglobulin proteins
-Centered around venule, with sharp demarcated edges
-Deposition of immunoglobins and activated complement at site of demyelination
-Resembles an antibody mediated process
-No defects in mitochondrail respiratory chain detected

Pattern III(~26% Lesions)
-Distal oligodendrogliopathy, diffuse lesions with variable inflammation and pronounced microglial activations
-Indistinct border
-Not centered around venule
-Striking loss of myelin associated glycoprotein
-No complement activation
-Pattern associated with hypoxia
-Dying back of oligodendrocyte
-Looks like white matter stroke
-Defects in mitochondrial respitory chain

Pattern IV(~1% of Lesions)
-sharp macrophage borders
-Degeneration and oligodendrocyte death in white matter
-inactive plaque and no remyelination 
  Myelin Stain       Myelin Stain    Myelin Stain   Macrophage
       (LFB)                MOG               MAG           stain (CD68)
 * = loss of MAG compared to LFB and MOG. 
Is this astericks not remyelination, which it looks like it to me?

Patterns 1 and 2 may suggest that myelin/oligodendrocyte is the target, while patterns 3 and
4 suggest the oligodendrocyte may be the target. In pattern 1,
macrophages likely mediate demyelination, whereas in pattern 2, antibody
and complement may contribute to demyelination and is more similar to the autoimmune models, whilst patterns 3 and 4 resemble viral, toxic, ischaemic models. However these latter two lesions are not common in people with SPMS, where the lesions are typically pattern 1 and pattern 2, Pattern III was detected in people with relapsing MS, but this stage responds to immunosuppression, so how do you reconcile this?. However, many pathologists do not agree with these classifications.
So it tells us that the disease process(es) in MS is/are complex.

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