Shrinking MS lesions – anything to take note of?

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Are you surprised that some MS lesions shrink in size?

It has nothing to do with quantum mechanics – Planck’s constant or Pym particles. However, it has been noted for a while now that in some individuals their MS lesions could shrink.

The prevailing hypothesis is that shrinking lesions represent resolution of the underlying inflammation or even possibly repair. Others believe, like other scars elsewhere, MS lesions also shrink in size over time.

The long and short of it is that nobody really knows.

So now a team in Germany have decided to study this phenomenon in greater detail. They looked at serial MRI scans from 144 PwMS at baseline (MRI 0), after 1 year (MRI 1), and after 3 years (MRI 3) – see figure 1 below.

Figure 1: Left, time point 1; middle, time point 2; right, white matter lesion changes with the following color coding: red, increased; yellow, unchanged; green, disappeared.

What they found was that the greater proportion of shrinkage occurred in those individuals with gadolinium-enhancing lesions (see Figure 2 below).

Since, enhancement is thought to be marker of acute inflammation, shrinkage of lesions is most likely to be due to a waning of the blood brain barrier leak and reduction in inflammatory activity in these lesions.

The authors ask if this is an intuitive or a naive notion? …the short answer to this is, I don’t know.

Figure 2: Upper panel: The relation of white matter lesion volume at MRI 0 with white matter lesion shrinking between MRI 0 and 1 is illustrated by a scatter plot. Patients showing gadolinium‐enhancing white matter lesions are illustrated by yellow dots, patients without gadolinium‐enhancing white matter lesions by blue dots. Lower panel: The same graph is shown for the relationship between white matter lesion volume at MRI 1 with decrease in white matter lesion volume between MRI 1 and 3

Brain Behav. 2019 Sep 26:e01417. doi: 10.1002/brb3.1417. [Epub ahead of print]

Prognostic value of white matter lesion shrinking in early multiple sclerosis: An intuitive or naïve notion?

Pongratz V, Schmidt P, Bussas M, Grahl S, Gaser C, Berthele A, Hoshi MM, Kirschke J, Zimmer C, Hemmer B, Mühlau M.

Abstract

BACKGROUND AND PURPOSE:

New or enlarging T2-hyperintense white matter lesions (WML) are associated with clinical disease progression in multiple sclerosis (MS). The prognostic value of WML shrinking is unclear. Assuming that waning of acute inflammation and repair processes would be the main drivers of WML shrinking, we aimed to assess the prognostic value of WML shrinking in early MS.

METHODS:

We retrospectively analyzed a cohort of 144 early MS patients with three brain MRI scans at baseline and after 1 and 3 years available. All patients were therapy naïve at baseline and 70.5% of them treated with disease modifying drugs at year 1. We determined the volume of WML shrinking between MRI scans, total WML volumes, number of gadolinium-enhancing and new WML, white matter (WM) and gray matter volumes at each MRI scan. Clinical disability was measured by Expanded Disability Status Scale. We performed the correlation analyses of WML shrinking with other MRI parameters and clinical outcome.

RESULTS:

White matter lesions shrinking was highly variable between patients and correlated with the initial number of gadolinium-enhancing WML and with WM volume decrease. WML shrinking was not associated with clinical outcome.

CONCLUSION:

We found no indication of a prognostic value of WML shrinking in early MS patients. WML shrinking seems to be related to waning of acute inflammation.

About the author

Neuro Doc Gnanapavan

10 comments

  • Muito bom

    Another group ( another study) demonstrate that disappearing lesions could be a not so good sign 🙂

    Why ? They are disintegrating (your brain) (our brains)

    “But the UB research demonstrates that it is the atrophied brain lesion volume, which results from disintegration of lesions, and not creation of new lesions or progression of brain atrophy, that more accurately signals progression of the disease”

    “Neither changes in number and volume of lesions nor the development of whole brain or central brain atrophy showed any predictive power in demonstrating which patients would progress to secondary progressive MS, either from initial presentation of the disease, called clinically isolated syndrome, or the next stage, relapsing remitting MS,” said Zivadinov.

    “The fact that atrophied lesion volume was the only measure that was predictive of conversion to progressive multiple sclerosis, and brain atrophy was not, is a major novel finding of this study.”

    According to Zivadinov, atrophied brain lesion volume is predictive of disease progression primarily because it reflects both inflammatory and neurodegenerative pathological processes, which together result in the disappearance of brain lesions into cerebrospinal fluid.

    They are dissolving 🙂

    “This study showed that atrophied brain lesion volume represents a robust marker for predicting conversion from relapsing-remitting to secondary-progressive stages of MS,” Zivadinov said.

    “Atrophied lesion volume can be measured with a pair of simple MRI scans,” said Zivadinov.

    https://medicalxpress.com/news/2019-09-mri-marker-disability-multiple-sclerosis.html

  • Muito bom

    Another group ( another study) demonstrate that disappearing lesions could be a not so good sign 🙂

    Why ? They are disintegrating (your brain) (our brains)

    “But the UB research demonstrates that it is the atrophied brain lesion volume, which results from disintegration of lesions, and not creation of new lesions or progression of brain atrophy, that more accurately signals progression of the disease”

    “Neither changes in number and volume of lesions nor the development of whole brain or central brain atrophy showed any predictive power in demonstrating which patients would progress to secondary progressive MS, either from initial presentation of the disease, called clinically isolated syndrome, or the next stage, relapsing remitting MS,” said Zivadinov.

    “The fact that atrophied lesion volume was the only measure that was predictive of conversion to progressive multiple sclerosis, and brain atrophy was not, is a major novel finding of this study.”

    According to Zivadinov, atrophied brain lesion volume is predictive of disease progression primarily because it reflects both inflammatory and neurodegenerative pathological processes, which together result in the disappearance of brain lesions into cerebrospinal fluid.

    They are dissolving 🙁

    “This study showed that atrophied brain lesion volume represents a robust marker for predicting conversion from relapsing-remitting to secondary-progressive stages of MS,” Zivadinov said.

    “Atrophied lesion volume can be measured with a pair of simple MRI scans,” said Zivadinov.

    https://medicalxpress.com/news/2019-09-mri-marker-disability-multiple-sclerosis.html

  • What makes the lesion white in the first place? Them being black makes sense as something has died – but not white like Tumors. Is it due to water? Or is it like a fibrotic patch?

    Sorry for the naive question.. We here a lot about lesions and how important they are, but not sure I know about why they start white and go black

    • Hi, the reference to white matter lesions comes from their location, which is in the white matter region as opposed to grey matter. The white matter is heavily myelinated, which gives it the white appearance. Also on MRI scans they appear white. At a tissue level the first ever description of them was seeing glial scars – from where derives the term sclerosis! When you sat in the lesions you find that they’re devoid of myelin, axonal loss and scaring (gliosis) and have immunological activation surrounding them.

  • NDG,

    “The long and short of it is that nobody really knows.”

    Without coming across as too rude, I do wonder what MS research has actually achieved over the last 50 years. The lack of knowledge about MS lesions is another example. When I was diagnosed some 16 years ago there was a lot of fuss about a paper from Prineas and Barnett (may have spelled these wrong) which was about the formation of early lesions. Nothing, to my knowledge has resulted from this work – nothing of benefit to MS patients.

    I was never a fan of the NMSS Promise 2010 programme which promised so much (eg neuro-protection therapies, re-myelination therapies). One of the programmes funded was to examine lesions. The research team identified 4 distinct types of lesions, but again nothing practical (to my knowledge) has come from this work.

    Prof G now talks about Slowly Expanding Lesions and chronic lesions, but no therapies are available to tackle these lesions (which are probably the cause of brain tissue loss and disability).

    I find MS research so frustrating – hundreds of researchers, lots of Professors, tens of thousands of research papers, but we still can’t point to one indisputable fact about this disease e.g. what causes lesions!

  • Are the lesions in MS the same lesions as people with AIDS develop on their skin?

    Are they blisters in the brain?

    What do these lesions look like when an autopsy is done on someone who had MS donates their body to medical science? Do they look like cold sores?

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