About the lesion's evolution

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About the lesion's evolution

Postby frodo » Thu May 25, 2017 12:12 am

The first damage that appears in white matter are the so-called "normal appearing white matter" (NAWM) areas. Myelin at these areas is already damaged, and at some point, they will turn into MS lesions.

There is now a new study that sheds some light into how the NAWM areas turn into lesions. They found three factors involved into the lesion develpment: N-acetyl-aspartate (NAA), creatine (Cr) and choline (Cho).

What they found is that "compared with NAWM, pre-lesional tissue had higher Cr and Cho" and that "pre-lesional tissue has higher NAA than lesions"

Source:
http://onlinelibrary.wiley.com/doi/10.1 ... 23647/full
Proton MR spectroscopy of lesion evolution in multiple sclerosis: Steady-state metabolism and its relationship to conventional imaging
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Re: About the lesion's evolution

Postby frodo » Tue Jun 20, 2017 2:17 pm

And other study about lesion evolution puts the blame in the cortical lesions. It seems that the damage present in the cortex spreads later to the white matter. The cortical damage is probably initiated by B-cells in the meninges. When disease turns SPMS, the B-cells develop into follicles.

In vivo detection of connectivity between cortical and white matter lesions in early MS

http://journals.sagepub.com/doi/abs/10. ... 8516671027

Results:

All patients showed inter-lesional WML connectivity (median 76% of WMLs connected to another WML; interquartile range (IQR), 58%–88%). On average, 52% of detected CLs per patient were connected to at least one WML (IQR, 42%–71%). Volumetric connectivity analysis showed significantly elevated cortical lesion ratios in MS patients (median, 2.3; IQR, 1.6–3.3) compared to null MS and healthy control datasets (p < 0.001).
Conclusion:

These findings provide strong evidence of inter-lesional connectivity between CLs and WMLs, supporting our hypothesis of intrinsic CL-WML connectivity.
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Re: About the lesion's evolution

Postby frodo » Sun Jul 09, 2017 4:32 am

More information about the NAWM and cortical lesions:

The relationship between cortical lesions and periventricular NAWM abnormalities suggests a shared mechanism of injury in primary-progressive MS

http://www.sciencedirect.com/science/ar ... 8217301663

They conclude: "Our data thus suggest that a common – and relatively selective - factor plays a role in the development of both cortical lesion and periventricular NAWM abnormalities in PPMS".

And there is also a report showing that some cortical lesions are vascular-related (gadolinium enhancement means BBB breakdown)

MRI evidence of acute inflammation in leukocortical lesions of patients with early multiple sclerosis

http://www.neurology.org/content/early/ ... 7.abstract
Last edited by frodo on Tue Jul 25, 2017 11:38 pm, edited 1 time in total.
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Re: About the lesion's evolution

Postby frodo » Sun Jul 23, 2017 11:30 pm

More information about cortical lesions:

Fibrin(ogen) and neurodegeneration in the progressive multiple sclerosis cortex

Source: http://onlinelibrary.wiley.com/doi/10.1 ... 24997/full

Objective: Neuronal loss, a key substrate of irreversible disability in multiple sclerosis (MS), is a recognised feature of MS cortical pathology of which the cause remains unknown. Fibrin(ogen) deposition is neurotoxic in animal models of MS, but has not been evaluated in human progressive MS cortex. The aim of this study was to investigate the extent and distribution of fibrin(ogen) in progressive MS cortex and elucidate its relationship with neurodegeneration.

Interpretation: For the first time, we provide unequivocal evidence that fibrin(ogen) is extensively deposited in progressive MS motor cortex, where regulation of fibrinolysis appears perturbed. Progressive MS cases with severe fibrin(ogen) deposition have significantly reduced neuronal density.

And just a thought, Could this be related to the lipoic acid effect?
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Re: About the lesion's evolution

Postby frodo » Mon Oct 16, 2017 12:29 am

About the early events in the demyelination process, it seems that axonal pathology is independent from inflammation:

In vivo characterization of cortical and white matter neuroaxonal pathology in early multiple sclerosis

https://academic.oup.com/brain/article/ ... -and-white

"These results suggest early demyelination with loss of cells and/or cell volumes in cortical and white matter lesions, with additional axonal dispersion in white matter lesions. In the cortex, focal lesion changes might precede diffuse atrophy with cortical thinning. Findings in the normal-appearing white matter reveal early axonal pathology outside inflammatory demyelinating lesions".
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