gray matter affected in earliest stages of MS

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Postby OddDuck » Sat Nov 20, 2004 6:44 am

Hi, bromley!!

More good questions!

Ok......again, I'll take a shot. Robin and Wesley (and others), hopefully will also add their comments.

Ok....memory loss associated with MS. Memory and cognitive processes in the brain are very strange complex mysterious things. Studies have been done and are still ongoing (not just in relationship to MS) about just how the brain "works". The most that can be ascertained is that the brain DOES work very similarly to an actual computer. (My guess is the reason why Wesley, Robin and I have such deductive reasoning abilities, it appears, is because if you noticed, we all are good with computers). When data is stored in a computer, it is fragmented and bits and pieces are or can be stored anywhere and everywhere on the hard drive. It "appears" that the data has been stored somewhere in one piece, but that is not the case (if you will recall, we used to even have to run a "defragment" program on our computers every so often to try to gather pieces of data together as much as possible). The same with the brain. Memory appears to be fragmented when it enters the brain. Bits and pieces of knowledge and memory are stored all over. There appears to be no rhyme nor reason that can be currently ascertained. Now, earlier I mentioned how the cerebellum at the base of your skull does the "processing". Think of that as the CPU part of a computer. Not only does it process and send messages regarding body "actions" to the other parts of the brain (i.e. various parts of white matter), it also sends out cognitive, memory and knowledge input to other parts of the brain.

It "appears" that as far as certain types of cognitive processes are concerned, some of those processes seem to be concentrated in the frontal lobe of the brain (white matter). Here is another good visual for you:

http://www.neuroskills.com/index.shtml? ... ntal.shtml

Since as we mentioned before, MS tends to interrupt processes in the white matter, if it interrupts processes in the frontal lobe(s), it's likely that memory, etc. will be affected.

As far as similarity between diseases............I know what you mean. Welcome to neurology. They overlap, don't they? That's why you see me say "where does one thing leave off and another begin"? It is definitely extremely difficult to put a boundary around any one neurological disease. There are only "slight" differences. And unfortunately, since most neurological diseases are still of a great "mystery", there may not be any good answers that can be provided.

Preprogrammed cell death is a regular process of the body that needs to be done. Cells in the body get old and need to die. You may have heard that the human body totally regenerates itself like every 7 years or so. Our bodies are constantly renewing and replacing our cellular structure. It has to. Otherwise, if the human body had NO way to regenerate, none of us would live very long at all, just speaking total lifespan. A few years at best. So preprogrammed cell death is a natural function of the body. Where the problem comes in is if this cell death process is "skewed" somehow. Hence, MS, Parkinson's, Alzheimers and many other neurological diseases will/may refer to some dysfunction or another of cell death.

Some main differences, though, between the diseases you mention are the biological locations that are affected. Again, that's putting it as simply as possible. MS targets specific minute cellular structures of the body (in the brain and spinal cord), Parkinson's results from dysfunction in different biological locations, etc. etc. Now, this gets very detailed and right down to microsopic minutia, but to keep it simple, what I've had to do is remember that it's not the terminology used to describe the physical result (symptom manifestation) from any particular dysfunction that matters, it's the biological location in the body that tells the difference between neurological diseases. And to go just one layer deeper on that, there are also small differences in which particular "process" in the body that is somehow dysfunctional that tells the tale. Parkinson's loss of function (i.e. tremors) appears to come from the body's almost total inability to create and utilize dopamine, and/or it destroys dopamine. MS's loss of function (tremors) appears to come from damage to a part of the brain that helps to control that type of movement (again, the message/transmission isn't getting to a part of the body quickly enough or clearly enough). The damage result "appears" the same from the outside (i.e. both have tremors), but the reason WHY is different.

And again, the same with "dementia". Alzheimers dementia comes from a different type of damage going on inside the body than what is happening with MS.

Now....having said ALL of that...........remember, the likelihood of tremors with MS being anywhere near as severe as the tremors associated with Parkinson's are so remote as to not be comparable. The same with dementia. You can't/shouldn't make a comparison between any RARE dementia that may be said to be associated with MS, as the same degree of dementia as what happens in Alzheimers. It's not comparable at all.

Are the researchers looking for "links"? I'd say yes, but so far, there doesn't appear to be too many, other than the fact that neurological diseases themselves overlap, simply because neurological diseases are isolated to the nervous system. That's the "link" that you can make. They are all diseases of the nervous system. It's a systematic link, not necessarily a "disease" process link. There are generalities, of course, such as dietary and supplement considerations if you have any type of neurological disease, but aside from that, so far, the minute details of the different neurological diseases are somewhat different from each other. But....it's still venturing into the unknown at this point in medical research. (Maybe that's why they come up with analogies all the time between medicine and space exploration! :wink: )

But we need to make sure that the ideas above are not forgotten - I would have thought that a professor of neurology looking for a Nobel prize would do well to pull together the excellent ideas exchanged above.


I think you'll find most of us agree with you there, bromley!! That's what you will see a lot of us say time and again. We even had a discussion on this website about the Nobel prize. And actually, I think you would be pleasantly surprised at how many people ARE assertively expressing our thoughts and ideas and questions to the medical community! :wink:

Deb

EDIT: I'm editing for typos again! :oops: :P
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Postby OddDuck » Sat Nov 20, 2004 6:46 am

Hey! Good morning, Robin!!! I'm just sitting here sipping my coffee (yes, I'm bad.......but only ONE cup each morning. Then I do my green tea. :lol: )

Wish I had a crumpet or something to go with it though! Send one over, will ya? :lol:

Deb
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Postby Sharon » Sat Nov 20, 2004 5:28 pm

Robin, Deb and Company,

What causes the weakness in the legs, etc? Is it because the muscle is not being "fired" 100% due to the disrupted signal from the white matter of the brain?

SharonR

Edit: Is the weakness caused by a deficiency of a nerve signal or is it because the lack of a signal?
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Postby HarryZ » Sat Nov 20, 2004 7:10 pm

Sharon,


What causes the weakness in the legs, etc? Is it because the muscle is not being "fired" 100% due to the disrupted signal from the white matter of the brain?


Muscle movement requires signals to move in both directions...from the brain and to the brain ...,when you have damaged nerves and the signals can't travel normally or even at all, you get the weakness. Of course, this happens over time and part of the weakness is caused by not being able to use the muscles properly...they may begin to atrophy. This is a very simple explanation and there is more involved to it but you get the general idea.
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Postby finn » Sun Nov 21, 2004 6:19 am

Sorry, time to leave the board.

-finn
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Postby OddDuck » Sun Nov 21, 2004 7:08 am

Hi, finn!!

Welcome back!

Is it already a proven fact that MS is primarily a demyelinating disease?


Well, good "catch", finn. (And I am addressing this directly and personally, as that was MY writing.)

I suppose I should have been even MORE literal in my statement. But I never stated that it WAS a "proven fact". OH...WAIT.....Damn, maybe I did!

Ok....clarification required if so!!!! (NOTE: Since intially writing this, I went back and double-checked my wording - clarification provided in second edit below - and my first assumption was correct. I did NOT state it as a "proven fact").

So far, according to the medical community, mind you, MS has "statistically" indicated that it is primarily a demyelinating disease.

Maybe I should have prefaced my discussions with "My understanding is", which I thought was a given assumption that anything I, or anybody, says is simply "my" or "their understanding"; and in this case is based on what the medical community presents to us (again a "given")......in my world, virtually next to nothing can be stated as a proven "fact" - from anybody -(but that's a discussion for a quantum physics or metaphysics message board, not this one). :)

So, let's say that right now, it is presented by the medical community to patients "at this point in time" that MS is primarily a demyelinating disease. (Why in the world would I have to state THAT so specifically, though?) So any subsequent words after that supposition (i.e. that MS is primarily a demyelinating disease) is derived from that initial assumption.

And yes, that's what we are also saying throughout all these threads. The fact (I use the term loosely) that there appear to now be other "patterns" of MS, that do not indicate that all patterns of MS are necessarily demyelinating. But even that is not known for "certain" yet.

As it stands right now, though, has the medical standard been changed as to the definition or description of MS? No. not to my knowledge. (I just get tired of having to personally say over and over before I speak to please remember that just because I personally say something, there's no reason for my posts to be given any more "weight" as it being "fact", as is given ANYBODY who posts and make "statements" on here. My way of speaking is no different than others'.) So, again, purely for clarification purposes........just because I (or ANYBODY) says something or speaks at all on any subject, does NOT make it fact.

What if changes in gray matter are the primary process, and different lesions (or lack of them) are the way that our system reacts against those changes?


Precisely. Lots of "what ifs" in MS, huh? Which I know you know, finn. :wink: I played the "if/then" game with my first neuro one time. The problem with that is, you can only "guess" at the "then" part of that.

If you want ME to "guess", I'd say "if" [above], "then" it looks like there would have to be new hypotheses formed, test results and methodologies re-evaluated and/or discovered, diagnostic criteria re-formulated, and MS research may need to take or consider a turn toward another avenue of study.

What if different pathological and clinical signs of the disease are related to the differences in patients' immune reactions against the primary disease process (or lack of immune reaction), not vice versa?


Yes, I have myriad "what if" questions, also. And what you are presenting here for discussion (in my viewpoint) is the current constant "autoimmune" vs "non-autoimmune" argument. This is one of the "what ifs" that goes into my frustration statements when I mention the fact that I wish (and me "wishing" is a "fact" that I can reliably state) they would run more tests on patients in the first place, and make more ongoing immune correlations as a general rule. As an example, and the first one here may not be directly associated, of course, with immune system function; but how often IS a patient given MRS (or other newer types of MR methodologies), and how often is an MS patient tested via ELISPOT to help determine what their immune system is doing at any given point in time? How often are the levels of interleukins and/or cytokines even measured? I BEGGED my neuro to run an ELISPOT on me to see what my immune system might or might not be doing, and to no avail.

Hence why MS research is still ongoing. Anybody can provide their own individual hypotheses on many things in MS, but that's still what they remain - hypotheses. Especially (again a common sense "given") when the hypothesis(es) is/are being presented on a discussion board by lay people without the ability to even have ACCESS to laboratory facilities, etc. on their own.

And I'm actually surprised you asked these types of questions, as I know you yourself, finn, create and present your own hypotheses and opinions regarding MS, etc. So...........(and I'm asking this in a light-hearted manner)..........was this a test? :wink:

Deb

P.S. Stick around now! Oh, yea....and finn. Never would I refer to YOU as THAT much of a "layman". :)

EDIT: I've made a few edits for clarification.

I guess my "manner" of speaking (I've been told I speak confidently - ?) may "appear" that I am attempting to present my viewpoints as "fact", but please remember that is not necessarily the case. Confidence in manner of speaking does not immediately equate to something being automatically presented as "fact". Thanks!!

SECOND EDIT: I was correct the first time above, before I made edits to this post. I initially said that I had not said that MS is primarily a demyelinating disease as a "proven fact". I was correct. My exact statement in another post was:

Multiple sclerosis is primarily a demyelinating disease; therefore, existing mainly in the white matter (affecting "transmission" of information from the brain).


Note that I did NOT say that 'It is a "proven fact" that Multiple sclerosis is primarily a demyelinating disease....' So my first response above that I did not say it was a "proven fact" was correct! Any inference at all that indicates that I did say that is therefore totally incorrect. Thanks!!!
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Postby finn » Sun Nov 21, 2004 7:43 am

Sorry, time to leave the board.

-finn
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Postby OddDuck » Sun Nov 21, 2004 7:59 am

:lol:

Well, I have to say that I personally agree with you on those points, finn. I'm somewhat excited over better MRI methodologies, myself!

And I apologize if it appears that I might have taken something a little "personally" (it's been a rough week or so), but please do not think I was insulted or offended. I wasn't. (Not with you, for sure.) I was just more concerned that I might be (or could be) misunderstood, is all. :D

And you KNOW I'm happy to see you! Always!!

Deb
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Postby OddDuck » Sun Nov 21, 2004 8:04 am

So, finn...........I have a "pondering" to express back............

So, what in your opinion might be the first steps that should be taken in order to come up with better or more reliable answers to those (and other questions) - assuming that a linear approach itself is even necessarily a valid one?

Deb

EDIT: You know, though, finn..........taking out my concern about being misunderstood and re-evaluating your initial "what if" questions,..........darn, I'd have to simply say "then" that means everybody has to start over from scratch! 8O

SECOND EDIT: And that leads us back to quantum physics and/or "quantum BRAIN"! HAH! 8O :wink: :)
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Postby OddDuck » Sun Nov 21, 2004 9:12 am

Ok...........sometimes I have to allow my mind to "work". Going back to one of finn's initial questions:

What if changes in gray matter are the primary process, and different lesions (or lack of them) are the way that our system reacts against those changes?


Assuming that the theories that gray matter is related to or indicative of "intellect" or "intelligence", if the changes in gray matter were the primary process, wouldn't one or "some" of the first disease presentations of MS be varying degrees of intellectual retardation or degeneration? And I'm not talking about "cognitive" issues - that's different than intelligence degrees or changes.

Allowing for the theory that gray matter relates to intelligence, then what is currently evidenced as disease presentation associated with MS would lend support to a fairly reliable hypothesis that changes in gray matter are NOT the primary event in MS.

Robin........Wesley.........it's about to get deep in here again. You two have any comments?

Deb
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Postby raven » Sun Nov 21, 2004 9:59 am

I don't think that demyelination and loss of gray matter are mutually exclusive. If we accept the contention that MMP-9 plays a major part in the pathogenesis (This is only my conjecture and as has been said by others no-one should assume that my contentions are fact). An over-expression of MMP-9 within the white matter can cause demyelination. When that over-expression occurs close to the BBB it can cause breakdown, infiltration of leukocytes and macro inflammation (i.e. visible to MRI). This would be in addition to causing over-expression of TNFa and IL-1b. TNFa and IL-1b can trigger apoptosis. Within white matter this apoptosis would affect the oligodendrocytes further enhancing myelin destruction. Within gray matter they can cause apoptosis of the neurons themselves. As a neuron dies it's axon also dies further increasing white matter damage.

I have not seen the association between intelligence and grey / white matter proportions. I would assume that the shift in proportions would be due to a greater number of interneurons whose axons are not myelin coated. A greater number of interneurons would theoretically increase your 'processing power'.

That said, I don't think you can separate intellect from cognitive ability. Also any changes would be far more difficult to detect than changes in motor function for example.

Am I more intelligent or less intelligent than I was 10 years ago? I know more than I did then, but have my reasoning abilities decreased since then? I don't know. This would be further compounded by the plasticity of the brain re-routing damaged pathways. This alludes to Bromleys question, how much gray matter can we afford lose? Who knows...

Robin
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Postby OddDuck » Sun Nov 21, 2004 10:15 am

Robin,

I'm dying laughing! (I think I love you!) NOT laughing at, of course.

Yep............"quantum brain", allright!

Deb

EDIT: Oh, again, by the way, I'm right there with ya!! :wink:

SECOND EDIT: We better stick with "classical mechanics"..... :lol:
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Postby raven » Sun Nov 21, 2004 10:27 am

I wonder what schrodingers cat would have to say about all this! :lol:

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Postby OddDuck » Sun Nov 21, 2004 10:31 am

That said, I don't think you can separate intellect from cognitive ability.


Or...............maybe you can:

cog·ni·tion ( P ) Pronunciation Key (kg-nshn)
n.

The mental process of knowing, including aspects such as awareness, perception, reasoning, and judgment.
That which comes to be known, as through perception, reasoning, or intuition; knowledge.


in·tel·lect ( P ) Pronunciation Key (ntl-kt)
n.

The ability to learn and reason; the capacity for knowledge and understanding.

The ability to think abstractly or profoundly. See Synonyms at mind.
A person of great intellectual ability.


in·tel·li·gence (n-tl-jns)
n.

The capacity to acquire and apply knowledge, especially toward a purposeful goal.

An individual's relative standing on two quantitative indices, namely measured intelligence, as expressed by an intelligence quotient, and effectiveness of adaptive behavior.

Source: The American Heritage® Stedman's Medical Dictionary
Copyright © 2002, 2001, 1995 by Houghton Mifflin Company. Published by Houghton Mifflin Company.


Main Entry: in·tel·li·gence
Pronunciation: in-'tel-&-j&n(t)s
Function: noun
1 a : the ability to learn or understand or to deal with new or trying situations b : the ability to apply knowledge to manipulate one's environment or to think abstractly as measured by objective criteria (as tests)
2 : mental acuteness —in·tel·li·gent /in-'tel-&-j&nt/ adjective —in·tel·li·gent·ly adverb


But that depends on what part of your brain logistically that you are using in order to "think". And/or which sub-division of consciousness you personally are utilizing at any given point in time to "think" (i.e. conscious, sub-conscious, or super-conscious mind). :wink:

Deb
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Postby OddDuck » Sun Nov 21, 2004 10:31 am

Oh, yea!!! The Cat!

Do we even know if he's dead or alive? ROFL!!!!!!!!!!!!!!!!!!!!!!!!!!!!! :lol: OR in how many parallel universes he exists in simultaneously?

Deb

EDIT: Apologies, folks. We got a little off-track here. :lol:
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