Lucchinetti pattern III and CCSVI

[frodo]

This is an old article but I found it just now. I found it specially interesting because CCSVI theory didn't still exists at the time it was published.

It says that the Lucchinetti pattern III could be produced by "a pathologic process similar to ischemia". The author besides hypothesizes two possible mechanisms: vascular impairment leading to defective microcirculation, and local production of toxins that alter the mithocondrial energy metabolism.

The original text: (available at http://www.ajnr.org/content/27/5/954.full)


Recent histopathologic studies of MS lesions, however, have revealed a great variability within lesions of different subjects with respect to the extent of inflammation, oligodendrocyte pathology, and neuroaxonal injury. Four different patterns of pathology with resulting demyelination have been observed in MS lesions: Type 1 are T cell-mediated and account for 19% of lesions where demyelination is macrophage-mediated, either directly or by macrophage toxins. Type II lesions are both T cell and antibody mediated and, at 53%, are the most common pathology observed in MS lesions.

This pattern results in demyelination via specific antibodies and complement. Type III represent the 26% of lesions and are related to distal oligodendropathy; degenerative changes in distal processes occur that are followed by apoptosis. Type IV is responsible for only 2% of lesions and results from primary oligodendrocyte damage followed by secondary demyelination. This latter pattern was observed only in a small subset of PPMS patients.

Of note, the pattern of demyelination found in type III lesions mimics that found in the early stages of WM ischemia and may therefore reflect hypoxic WM damage. A pathologic process similar to ischemia could be induced in inflammatory conditions by 2 mechanisms: vascular impairment leading to defective microcirculation or local production of toxins that alter the mithocondrial energy metabolism.

[1eye]

Somebody please clue me in to whether we are talking hypo or hyper oxygen here because it seems a bit ambiguous to me: hypoxic means low oxygen, right? What toxins are we talking about? Anybody ever see one?

[frodo]

Somebody please clue me in to whether we are talking hypo or hyper oxygen here because it seems a bit ambiguous to me: hypoxic means low oxygen, right? What toxins are we talking about? Anybody ever see one?

This means hypo. It does not stand for hypo-oxigen, but for "hypoxia of oxigen" instead.

https://en.wikipedia.org/wiki/Hypoxia_%28medical%29

By the way, pattern III was one thought to be a pre-active lesion (not anymore)

Neuromyelitis optica lesions may inform multiple sclerosis heterogeneity debate

https://onlinelibrary.wiley.com/doi/ful ... /ana.23621

Early active demyelinating NMO lesions may show complement within macrophages and oligodendrocyte apoptosis associated with a selective loss of minor myelin proteins, in addition to typical NMO features. We hypothesize these findings occur simultaneously only in a subset of active demyelinating NMO lesions.

These observations plausibly explain the findings of Barnett and Prineas and further support the concept of interindividual heterogeneity in MS.

[1eye]

The reason I am confused is because there has been a lot of work showing that there is not a shortage of oxygen (which, by itself, might point to a drainage problem), but Virtual Hypoxia due to possibly mitochrondrial problems which result in inability to consume (burn) oxygen in the brain. So perhaps some work need to be done to show whether this hypoxic condition is also virtual...

[Cece]

The reason I am confused is because there has been a lot of work showing that there is not a shortage of oxygen (which, by itself, might point to a drainage problem), but Virtual Hypoxia due to possibly mitochrondrial problems which result in inability to consume (burn) oxygen in the brain. So perhaps some work need to be done to show whether this hypoxic condition is also virtual...

An actual shortage of oxygen would worsen an existing case of virtual hypoxia. It could be both. Lucky us.
I haven't read the article yet, but I will as it looks like a good find.