Lesions, Lesions and more Lesions!

[Quixotic1]

LESIONS! LESIONS! LESIONS!

Life Is More Than A T2 Hyperintensity.

This blurb is long overdue, but is prompted by Julie's (Sarahsmom) question about the role of Gray Matter lesions in MS.  I am trying to learn as much as I can about this topic.  Currently, my understanding is still growing, so this will just have to be an introduction into the emerging world of lesions beyond the T2 Hyperintensities that seem to limit our (and our doctors') view of our disease.

First, when you look at the brain, either directly or in MRI images, you see that the outside has a layer of denser cells.  These are the bodies of the cells of the brain.  They have extremely complex communications with surrounding cells via short finger-like projections called dendrytes.  The gray matter is the real computer of the brain - you could say it is the "thinking part of the brain."   Every cell in the gray matter sends a longer axon deeper into the brain to communicate either with another brain cell or with a part of the body.  These long fibers (axons) have a whitish, fatty sheath insulating them called myelin.  All of these fibers running and communicating with distant parts is called the White Matter, because it appears white from the myelin.

Ninety-nine percent of the talk about the damage in MS centers around the bright lesions seen on the T2 & FLAIR views of our MRIs.  It seems that whether we have MS is dependent on how many of these we have, how big they are and where they are located.  Listening to so many of our neurologists, if we don't have the proper T2 Hyperintense lesions, then we don't have MS.  These lesions also seem to dictate how our disease is, or is not, progressing.  If we have new lesions then the disease is worsening.  If we have a symptom, but there is not a lesion to explain it some neurologists doubt the validity of the symptom.  Our doctors may gage disease activity by how many new lesions we get and how many disappear.  Some neurologists actually presume to tell us that the MRI picture is 1000% of the truth about our disease.  If we have  No Lesions the we have NO MS.  If there are  No New Lesions, then our disease is not active or is not progressing.

The T2 Hyperintensities, as we understand them, do represent those areas of demyelination on the neurons (nerve fibers).  The appearance of enhancing lesions on the T2 images does correlate with appearance of new symptoms and new relapses.  This is the immune inflammatory part of MS. And all of the current therapies are aimed at reducing this immune inflammatory process.

IS THAT ALL THERE IS?

Well, we all know that it is not, even though a few neurologists seem to think that the T2 lesions explain everything about our disease.  We know that a certain number of people with MS do not have T2 lesions.  We know that we can have symptoms that are very real, yet do not have a visible lesion that corresponds to them.  We know that we can have a increasing disability without an increase in our "lesions."  And we also know that some of us have "failed" a DMD based on our rising symptoms, yet the brain MRI T2 lesions do not show a great change.  So we have a lot of clues that there is more to Multiple Sclerosis than the T2 lesions seen on our regular MRIs.  Currently research is telling us more and more about three other areas of damage in MS.  These are 1) the "Black Holes" seen in the white matter on the T1 images of the MRI,  2 )  Lesions in the Gray Matter of the brain and spinal cord, 3)  Abnormal changes in the Normal Appearing White Matter (NAWM) of the brain.

BLACK HOLES

We have talked before about the areas called "black holes" that can appear on the T1 views of the MRI.  These are areas that are hypointense (less dense) than the brain tissue around them.  These are places where the damage to the axon, the long nerve fiber,  is so severe that it has been destroyed - a process known as axonal degeneration.  These nerves can no longer remyelinate.  They have died, shrunk and been scarred down or reabsorbed by the body leaving an area that is mostly empty.

Are these nerves just ones that had such severe attacks on their myelin that they couldn't recover and then died?  Actually, no.  Researchers have shown clearly that the majority of these "black holes" suffered their damage without any earlier inflammatory damage to their sheaths.  For some reason, still not completely understood, they have suffered direct axonal death.  We also know that this direct axonal degeneration is known to occur very early in the course of MS, often before any of the typical T2 lesions has appeared.  These areas of brain cell death are invisible on the regular MRI until so many nerve fibers have died off that the areas are big enough to see.

Black holes are felt to represent a good part of the cause of the ongoing disability that characterizes so much of MS.  Doctors who treat MS who noticed for a long time that MS is made up of Relapses and Remissions, but that there is also a progression of real disability that progresses - in the "background" - independent of the relapses.  That is, the relapses alone do not explain the progression of disability.  Relapses also do not explain the appearance and worsening of brain and spinal cord atrophy.  The brain actually shrinks in volume.  On the MRI this shows up as larger ventricles filled with CSF fluid and as a widening of the in-and-out wrinkles (called sulci) on the outer surface of the brain.

We also know that people with PPMS often have far less inflammatory activity in the course of their disease.  Their T2 lesions are often much smaller and they have fewer enhancing lesions.  Yet they have more brain atrophy and it appears earlier.   The reason for this is that they often have many more (and larger) T1 Black Holes.  So, in people with PPMS, there is more of this direct nerve destruction that occurs outside the immune inflammatory process that makes the T2 Hyperintense lesions.

Continued in the next post

[jensequitur]

Has this been turned into a Health Page yet?

[Lulu54]

*bump*

[tot_teacher]

Quix -

I found the health pages and a wealth of info ... printed it out to add to my pleasure reading when I get a moment or two ... thanks

- Alisa

[Quixotic1]

From my reading to date the only thing that I have able to confirm is that the gray matter lesion volume is highly related to cognitive disability.  One group looked at it with regard to fatigue and were surprised to find no relationship.

Alisa -  For your notebook.  Have your read some of the Health Pages on MRI's?  A few of them have some basic info also.

And, Thank you ALL very much for your praise.  It really did make me feel good, because I didn't think I was quite ready to writie this and was truly not sure if I was saying what you all wanted to know.  I have another blurb planned soon to describe some of the different MRI techniques - especially fMRI or functional MRI also known as MRI Spectroscopy.

quix

[young at heart]

QUIX,

VERY NICELY WRITTEN AS USUAL, ZILLA AND I HAD A SIMILIAR CONVERSATION ON THE PHONE THE OTHER DAY THAT THE CORRECT NEUROLOGIST ARE FINALLY ACCEPTING GREY MATTER LESIONS AS PART OF THE DISEASE.

THANK YOU

T-LYNN

[Tahiri_Veila]

Wow can you send this to all my old neuro's.  JK! I just show no normal lesions and all of the mimics are ruled out except fibro which just doesn't fit. (Not that I want MS).  It just makes me wonder if the problem it that the damage being done is not visible to the MRI's of today.
Tahiri

[GrannyJo6]

Add my accolades! Nice and easy to understand with just gobs of info! (Gobs being a highly technical term!) Very informative - thanks! Granny Jo

[Sarahsmom46]

Now that was so much easier to understand than what I was trying to google and look up on my own.  Thanks so much for doing the research and putting it in language we can all understand.  

But, I have one more question...If we do have lesions in the gray matter that are not visible, what might we see other than cognitive issues that would hint at the symptom may be coming from a GM lesion?  Just wondering.

Thanks again.

Julie

[tot_teacher]

Awesome Job, Quix !

This will fill the gap in my research notebook titled "MRI's for Dummies" which is currently empty.  Thanks for the easiest explanation that I've personally come across in my search ( never-ending ) for ANSWERS .

Thanks !

Alisa

[jensequitur]

Excellent stuff, as always...  Something else to remember - they've found that the brain with MS responds differently to the T2 MRI signal - there's a part of the brain that 'jumps' differently from normal people's brains during the MRI, even though the results may not show lesions in that area.  It shows that there's activity going on in the brain, even without lesion formation.

[doni54]

Fantastic!!! I would never expect any less, you never let us down.  Thank you for your hard work.

doni

[sllowe]

This is a masterpiece! And, there will be more to come! We are so spoiled.

Well done! Better than well! It's superb!

Thank you so much Mama Q!

-Shell

[OperaMBA]

This is awesome.

I am copying it to a word file to save!  

Bravissimo!

[Lulu54]

Wow Quix - great explanation.  I trust you will post this as a HP so it is readily accessible to everyone looking for information.  Bravo!! - Lulu

[biowham]

Wow, Quix. Nicely written, nicely explained. Good stuff. Thanks for working this up. I can see that there's been a lot put into it, and I know everyone is going to get a lot out of it.

Bio

[Quixotic1]

(con't)


GRAY MATTER LESIONS

Now we know that there are many lesions in the gray matter also, even early in MS.  The problem is that our regular, or conventional, MRIs do not show these gray matter lesions well at all.  In order to see these gray matter lesions we have to use newer MRI techniques that are used in research, but not usually available to the doctors in practice.  These techniques include "Magnetization Transfer" (MT MRI) and "Diffusion-Weighted" (DW MRI).  There are many others.  There are all miracles - in that I cannot really understand what they do - but they do it anyway, lol.

A heavy load of gray matter lesions is associated with greater cognitive disability - this is what interrupts our thinking, our attention and our memory.

Gray matter lesions have a relationship with the number and volume T2 Lesions.  Since the gray matter is the area where the cell body of the nerve fibers is, then we think that GM lesions may represent the final death of nerves which suffered severe demyelination from which the nerve could not recover.

Gray matter lesions occur very early in MS and it is hoped that with better ways to visualize these lesions we will be able to use information from them to diagnose MS earlier.  One of the studies I read showed that GM lesions were very numerous, surprisingly so.

Also,  we can view the GM from the standpoint of which areas are active during certain tasks, an MRI technique called "functional" MRI or fMRI.  We can see that there is often a large activation of the nerve cells around a lesion indicating the attempt of the brain to compensate for a lost area.  This is part of the process of using other areas of the brain to perform a lost ability - the process known as "Neuroplasticity."  In fact, when patients with optic neuritis were studied using fMRI, those with a larger area of activation in the visual center of the gray matter had better recovery from their visual deficits, than the patients with less.  The brain actually can reorganize itself to compensate for injury.


NORMAL-APPEARING WHITE MATTER (NAWM) LESIONS

When the neurologist points to there area around the T2 lesions and says "Now, this is the normal part of your brain,"  it isn't technically true.  It appears normal on the conventional MRI image, but studies using other MRI techniques, like functional MRI show different.  Even in very early MS disease we can see that there are changes in the normal appearing brain tissue, that show changes in metabolism, that show some of the chemicals that result from injury and show a change in the normal patterns of  nerve activation.

These changes in the NAWM are seen at the very earlist stages of MS, such as before it can be definitely diagnosed in the person with CIS, or Clinically Isolated Syndrome.

So, we can see that Multiple Sclerosis is a disease that involves almost all of the tissues of the central nervous system.  It is made up of FAR more than the "MS Lesions" that we always talk about.  This is why our disease seems so much more complicated than our MRIs might show.  It is!  When the newer imaging techniques become more available to the doctors out in practice we should see less misunderstanding.  Then all  doctors should see that the current MRI image - no matter what the strength - is not the sum total of our disease.

Quix