MS and Brain Grey Matter Atrophy
A bombshell struck the MS research/treatment sector just this past summer 2015 when it was reported that Dr. Jonathan Kipnis of the University of Virginia had made the totally unexpected discovery that lymphatic vessels drain the brain. Far from being “immunologically privileged” (that is to say without an immune system) the brain is drained by lymphatic vessels which parallel the draining veins. White matter lesions imply as much an immune system DEFENSE of injury to the brain/central nervous system as a pathological process to be suppressed.
This is a major discovery discussed in many prestigious scientific publications including Scientific American. www.scientificamerican.com › ... › Mind Matters.
What does this mean for MS? That the immune system represented by the lymphatic vessels works inside the brain to keep it healthy and suppressing it will likely be harmful. This provides the physical basis for Prof Michal Schwartz’s finding “that immune cells are pivotal for CNS neuroprotection and repair”.
Dr. Kipnis’ discovery of lymphatic vessels in the brain provides the missing factor which reinforces the work of Dr. Maiken Nedergaard, Professor at the University of Rochester, and Co-Director of the Center for Translational Neuromedicine. (She earlier spoke of a "plumbing system" that piggybacks on the brain's blood vessels” without realizing that this “plumbing system” is in fact composed of lymphatic vessels.)
http://www.urmc.rochester.edu/news/stor ... fm?id=3956
And finally we arrive at an understanding that white matter lesions may be less a worry than grey matter atrophy, a shrinking brain which can only mean increased disability.
The entire MS Neurology industry so preoccupied with suppressing lesions on the myelin sheath has been hit in the head.
Already they were aware of “the so called clinicoradiological paradox: Abnormal spots on the MRI often don’t manifest in physical or cognitive symptoms.” See my blog post March 2, 2015 and article dated April 2012. http://www.msdiscovery.org/news/news_sy ... -meets-eye)
In reality MRI scans of white matter lesions are limited indicators of the MS patient’s condition or progression.
The GOOD NEWS is that the progression of grey matter brain atrophy appears to correspond with progression of disability, AND, this atrophy can be measured on an MRI brain scan with a simple ruler. So what are we waiting for?
And the VERY GOOD NEWS is that MSers can help themselves by preventing or reducing this atrophy and theoretically can see the results of their efforts on yearly MRI scans (for example).
In conclusion, every effort must be made enhance fluid circulation throughout the central nervous system, stop any blood reflux, enhance cerebrospinal fluid circulation, stop the relapses and nourish the grey matter as well as the myelin sheath, the earlier the better. Optimal nutrition, supplements, fluid circulation therapies, functional body manipulation, and venoplasty itself if venous stenosis is serious all serve this end.
I am now going to quote directly from a discussion on the ThisisMs.com website triggered by a post by 1 eye on Jan 12, 2016 5:13 p.m. titled “Measuring MS” under General topics.
“http://www.smw.ch/content/smw-2013-13887/
In this document, referred to by Ms. Beal, also called "cheerleader", in at least two posts here (see http://www.thisisms.com/forum/chronic-cerebrospinal-venous-insufficiency-ccsvi-f40/topic27228.html#p238800 ), there is clear evidence for the existence of a set of measurable rates of change in various brain structures in MS, some of which are unique to the MS phenotype.
These measurements give us a clinical non-destructive way of distinguishing these variants of the disease. Various statements have been made about the lack of efficacy of DMDs on the progressive forms of these phenotypes. There may actually be efficacy, especially if atrophy is measured.
If the primary measurable effect of multiple sclerosis is brain atrophy, and if it is measurable using an ordinary ruler, why is it not a standard practise to measure it?
It cannot be true that atrophy is of no consequence. Even if it can be shown that there is no statistical relationship between atrophy and some other currently fashionable clinical measures, surely atrophy itself is the primary undesireable , measurable consequence of the disease. Other details are of less consequence, including broken neurons. The more a brain shrinks, the less possible it is to retrain it.
As an MS patient, there are two related pieces of information that are vital to me.
Across all the MRIs I have had done,
1. What is the current state of my various affected brain structures?
2. What is my rate of atrophy in these affected brain structures?
In addition, the effects of various Disease Modifying therapies on the mathematical derivative, or acceleration of these various rates of atrophy is of extreme interest to MS patients, so they can assess which of these therapies can best slow it down. The required measures can be arrived at using three or more brain MRIs. Each MRI has one data point for the size of each affected atrophic structure. The more MRIs, the more detailed and certain the resulting assessments will be, of atrophy, and of treatment success.”
1 eye is referring to an article in Swiss Medical Weekly dated 21 November, 2013.
Review article: Medical intelligence | Published 21 November 2013, doi:10.4414/smw.2013.13887
Cite this as: Swiss Med Wkly. 2013;143:w13887
Quote:
Brain atrophy: an in-vivo measure of disease activity in multiple sclerosis
Ernst Wilhelm Raduea, Kerstin Bendfeldta, Nicole Mueller-Lenkea, Stefano Magonc, Till Sprengera,b,c
a Medical Image Analysis Centre (MIAC), Basel, Switzerland
b Department of Neurology, University Hospital Basel, Switzerland
c Division of Diagnostic and Interventional Neuroradiology, Department of Radiology, University Hospital Basel, Switzerland
Summary quoted from the article:
Summary Multiple sclerosis (MS) has traditionally been considered to be primarily an inflammatory demyelinating disorder. Nowadays it is recognised as both an inflammatory and a neurodegenerative condition. This recognition is reflected in the development of new disease-modifying therapies that may offer the potential to reduce axon damage, either by inhibiting neurodegeneration or by promoting endogenous repair mechanisms. Since there is only a limited correlation between the clinical features of MS and findings on conventional magnetic resonance imaging (MRI), for the evaluation of such therapies new outcome measures are warranted. Grey matter atrophy occurs in the earliest stages of MS, progresses faster than in healthy individuals, and shows significant correlations with MRI lesion load, cognitive function and measures of physical disability; indeed, brain atrophy is the best predictor of subsequent disability and can be readily measured using MRI. Furthermore, it is becoming clear that currently available therapies differ in their effects on brain atrophy, and this may have important implications for the management of MS. New MRI techniques and advances in software development offer an opportunity to extend brain atrophy measurements beyond research studies to the routine management of MS patients.
Key words: brain atrophy; cerebral cortex; drug treatment; magnetic resonance imaging; multiple sclerosis; thalamus"
The discussion develops on This is MS as follows:
Dr. Geoff Jan 13, 2016
“So, if a simple measurement of brain atrophy is a good measure of MS severity, and if repeated measurements are a good measure of disease progression, and if - as the Swiss study shows - this leads to a direct comparison of the effectiveness of the various DMTs, guess what will happen? Now guess the response from the company that produces the least effective DMT.
Of course, this could be used to compare other things, if used over several years. Diets for example, CCSVI treatment versus DMTs, and there are a lot more.
And the downside? Someone will need to pay for annual MRI scans!”
Geoff
Cheerleader responds on Jan 13, 2016
Thanks for linking this info on the big boy board, 1eye
I began looking at biomarkers for MS progression when Jeff was diagnosed in 2007, after his neuro mentioned that white matter lesions weren't the best correlate for disease progression. I wondered what was?
Over the years, I've followed Dr. Zamboni's research (obviously, as my husband Jeff was the first North American treated for CCSVI) but also the BNAC team in Buffalo, since I met Dr. Zivadinov at the very first CCSVI conference in 2009 in Bologna. BNAC gets funding to image the brain and help pharma understand if/how their drugs are working. And the focus from white matter lesions to gray matter atrophy, specifically the thalamus, began to get more attention in Buffalo.
Almost all of BNAC's pharma funded research is now looking at thalamic atrophy in MS.
This blog post has the links to research, and a link which explains the use of measuring the width of the third ventricle and the thalamus as biomarkers for MS progression. As we all know, disability is not simply a measure of 25 timed walk or EDSS, as cognitive issues can be just as detrimental as physical ones.
http://ccsviinms.blogspot.com/2016/01/t ... ssion.html
The correlation of thalamic atrophy also makes sense in terms of understanding progressive MS---as loss of gray matter is found to continue during the progressive phase of MS. Indeed, gray matter atrophy is the only biomarker that begins with CIS, and ends at the final stages...
Fire away with questions, thoughts, debate, contrary research---but make sure to first check out the blog post, and see if your question is answered there. Will save time/energy here.
http://ccsviinms.blogspot.com/2016/01/t ... ssion.html”
On Jan 13, 2016 Cheerleader continues
But these MS MRI techs are talking about using thalamic atrophy in combination with third ventricle widening in terms of being the best biomarker for MS progression. I think their calculations make sense--it's very specific. Check out the whole paper.
Quote:
Thus, there is a huge need of a methodology suitable to be applied in daily clinical practice in order to estimate GM atrophy in a convenient and comprehensive way. Given the thalamus is the brain structure found to be more consistently implied in MS both in terms of extent of atrophy and in terms of prognostic value, we propose a solution based in this structure. In particular, we propose to compare the extent of thalamus atrophy with the extent of unspecific, global brain atrophy, represented by ventricular enlargement.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4144089/
cheer
On Jan 14, 2016 cheerleader continues
Two researchers who are members of the ISNVD, Zivadinov and Minagar, collaborated on a paper.
It explains thalamic atrophy and MS and summarizes the research-
Quote:
Thalamic pathology, similar to the cortical pathology, appears to be present in MS from very early on, including at the CIS stage and in pediatric MS. In the progressive phase of MS, which is poorly explained by focal inflammatory WM demyelination, cortical and subcortical GM pathology including neuronal and axonal degeneration are the likely substrates for accumulating cognitive and motor dysfunction that characterizes long-standing disease.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589190/
Dr. Minagar is going to be presenting on "MS as a vascular disease" at the ISNVD conference in April.
http://isnvd.org/sites/default/files/IS ... 1-2015.pdf
It is no coincidence that the researchers speaking out on thalamic atrophy and MS are also involved with the ISNVD and looking at MS as a vascular disease.
Why? http://ccsviinms.blogspot.com/2012/01/i ... -know.html
cheer”
ElliotB adds on Jan 15, 2016-
“How To Stop Shrinking Your Brain And Improve Your Thought Process"
http://www.medicaldaily.com/knowledge-b ... ess-302450
Imagine, improved diet, exercise, supplements, and proper sleep can all help your brain - what a novel idea!”
On January 16, 2016 cheer rejoins
“Yup! Great link, Elliot. So much we can do to maintain gray matter.
Here was my list of what to do on "Gray Matters" Written and put on line in 2012: Links to research included!
https://www.facebook.com/notes/10151031434857211/
Quote:
1. eat fish or take an omega 3 supplement
2. exercise. walk if you can, swim, practice seated yoga, dance, bike, move.
3. discover a new interest-- a foreign language, knitting, oil painting, floral arranging, cooking, juggling.
4. get vitamin D from sun and/or supplement
5. meditate
6. get plenty of good sleep, and take naps.
7. listen to music...even better, sing along or play an instrument.
8. read a book or join a book club
9. eat Indian food, or take a curcumin supplement. If curcumin is contraindicated for you, you can skip this one
10. hug often. A pet, a grandkid, a spouse, a tree, a friend--yourself
“cheer” goes on to explain to 1 eye
Everything I recommended to improve gray matter health has published reseearch behind it.
I will copy over all the lnks, because I know you don't like going to other pages, like the one Iinked https://www.facebook.com/notes/10151031434857211/, but I don't make it up. I merely compile research...never claim to be anything more than an interested layperson who has been looking at the connection of MS to gray matter atrophy for a few years now....
1. eat fish or take an omega 3 supplement
http://www.ncbi.nlm.nih.gov/pubmed/17574755
2. exercise. walk if you can, swim, practice seated yoga, dance, bike, move.
http://www.ncbi.nlm.nih.gov/pubmed/19560443
3. discover a new interest-- a foreign language, knitting, oil painting, floral arranging, cooking, juggling.
http://journals.plos.org/plosone/articl ... ne.0002669
4. get vitamin D from sun and/or supplement
http://yaledailynews.com/blog/2015/11/1 ... -patients/
5. meditate
http://newsroom.ucla.edu/releases/how-t ... rain-91273
6. get plenty of good sleep, and take naps
http://www.ncbi.nlm.nih.gov/pubmed/24346259
7. listen to music...even better, sing along or play an instrument.
http://www.medicalnewstoday.com/articles/246675.php
8. read a book or join a book club
http://www.ncbi.nlm.nih.gov/pubmed/25203270
9. eat Indian food, or take a curcumin supplement. If curcumin is contraindicated for you, you can skip this one
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527619/
10. hug often. A pet, a grandkid, a spouse, a tree, a friend--yourself
http://opinionator.blogs.nytimes.com/20 ... love/?_r=0
What if there is no "fix"? What if the "cure mentality" keeps us from addressing the things we can change today?
http://ccsviinms.blogspot.com/2014/06/t ... ality.html
Preserving and enhancing gray matter is real. Neuroplasticity is real. It may well be "the fix." Read Norman Doidge's new book, The Brain's Way of Healing...be encouraged and inspired. http://www.normandoidge.com/?page_id=1042 Outlive that solar contract!!! Outlive the fix!
xoxox,”
cheer
On Jan 17 1eye refers to:
Proposed method for measuring dRA, or delta Rate of Atrophy:
http://sullivanweb.me/pdfdocs/atrophy-3.pdf
This link refers to the following excellent article. I’ll quote it even though I don’t know the author’s identity. 1eye explains the calculations thereafter.
“I do not think we are keeping complete records of atrophy, which can describe the progress of MS disease. We can also use these records to demonstrate treatment success.
I propose an accurate measurement of brain atrophy in an area of white or grey matter known to be subject to it. A location is measured using bone as a reference point, say the top of the skull, or the point of a tooth. This reference is used to measure the size of the organ of interest, at a given MRI slice. As much as possible a reproducible location is used to make a size measurement.
The series of MRI measurements are repeated at intervals separated by at least a year. One MRI measurement gives the current size at a given location, of the given organ. For example the size might be measured each time to 0.5 mm accuracy.
The reason for making series measurements at the same latitude and longitude of a brain, is to assess any changes in size. That will tell us whether the organ has grown, shrunk, or stayed the same size.
The first measurement tells size alone. The second, in combination with the first, should reveal the current rate of atrophy, at the chosen location, expressed in millimeters per day. The third measurement, when compared with either of the first two, would also show a rate of atrophy.
Comparing MRI-1 and MRI-2 you get the Rate of Atrophy (RA) over the time frame t2 minus t1. Call this measured rate RAa. Comparing MRI-2 and MRI-3 you get the RA over the second interval t3 minus t2. Call this measurement RAb.
You can also, by comparing MRI-3 with MRI-1, confirm the RA at t3. Call this rate RAc.
These measurements give the organ’s size changes over the interval between the first two MRIs as well as the size changes between the second two MRIs. Using the overall time between first and last measurements will produce a measurement of the organ’s size changes over the interval between them.
Using calculated values in the three measurements you can produce a table:
MRI number organ size (mm) time of MRI RA (mm/day)
1 xx.xx DDMMYY hh:mm:ss 0.0 at t1
2 yy.yy DDMMYY hh:mm:ss RAa at t2
3 zz.zz DDMMYY hh:mm:ss RAb at t3
You can compare the atrophy rates at t2 and t3 to produce a rate of change of atrophy rates between the last two MRIs, in millimeters per day per month, for instance. The way to calculate this is to subtract RAb from RAa, producing delta-RA, or dRA. This will be positive if the organ’s atrophy rate has worsened, 0 if there was no change, and negative if there has been a slowdown of the rate of atrophy.
The overall measurement from t1 to t3 is a rate of atrophy that is more averaged, over the entire three years.
dRA is the more useful measure, showing change from one year to the next.”
On Jan 20, 2016 1 eye wrote
So here's a picture:
http://sullivanweb.me/pdfdocs/atrophy-4.pdf
This hypothetical patient shows -8.3 um atrophy per day in the first interval, and the atrophy changes such that the first interval's atrophy is partly reversed at a dRA of +0.85 um/day/month.
This measurement represents partial regrowth of brain matter at the third MRI at t3, which had previously deteriorated by the time of the second MRI at t2.
OK, so I did the unthinkable: I bumped and re-posted on my own thread. But I just wanted to say: the result of this measurement is a direct quantitative measurement, which at least is an analog to, and at best measures MS directly, puts a number to a patient's either improvement or worsening. Healthy controls should show dRA (delta Rate of Atrophy) = 0.
This measurement verifies with counting lesions, black holes, EDSS, and any other measure of MS. It can be done as a sanity check to every purported treatment improvement. A good treatment either reverses, slows down, or stops the disease. This one measurement can put a number on any of those changes, or show very clearly that there has been no change. Qualitative descriptions of these conditions is not good enough, when we are using machines that cost upwards of $30 million, with modern imaging, storage, and computing power.
If their physician won't do it, patients can actually do that same measurement for themselves, using whatever measuring tools (a ruler of some kind) are at their disposal. All you need are three time-separated MRIs. These are available: in most cases, the patient owns them.
See also http://sullivanweb.me/pdfdocs/atrophy-3.pdf
and http://sullivanweb.me/pdfdocs/atrophy-4.pdf
The Ottawa Hospital has some of my MRIs. In the one I had in 1997 the radiologist reported an atrophic corpus callosum. Along with the one I had in 1996, that forms a complete baseline RA measurement. I would like to see the dRA at my corpus callosum from every MRI I have had since (there have been many).
In the same discussion I eye also explains the calculations as being simple arithmetic. Excellent work.
I will need to revise my main paper in keeping with the brain atrophy issue.
I believe it perfectly reasonable to insist on an MRI of one’s brain grey matter/thalamus, and then embark on the healing programs outlined in my site – see 5 Steps to MS Health for instance, or Matt Embry’s program, and then continue with periodic MRI’s that monitor the brain’s condition. At least now there exists a physical, material basis for monitoring one’s MS progression, and also the possibility of being encouraged to continue a program that may appear tiresome.
UPDATE JANUARY 31, 2016
1 eye has just answered my query about the identity of the wonderful sullivanweb articles. He has identified himself as CHRIS SULLIVAN. He is Canadian and a well informed reliable contributor to the Thisisms.com site.
1 eye Jan 24, 2016
Sorry. You cannot find that link to sullivanweb.me anywhere (that I know of) except right here in this thread. There might be something close on my computer. Chris Sullivan is apparently the alter ego of 1eye, when he is at home. It's not really for publication anywhere, just a post to TiMS that ran astray; however the picture shows what the dRA is, and how you might use it to assess how one is doing after some kind of intervention. Atrophy is either worse, the same, or better, and dRA says how much, if it's not 0. If it is, you are young and healthy.
The clue is in the units: the hypothetical patient is getting better (just because of the sign), and the speed of the improvement is increasing, by as much as 0.85 um per day, every month since the intervention.
P.S. Sullivan is Gaelic for "one-eye".
Tags: Multiple Sclerosis treatment, MRI, Grey matter atrophy, Thalamus,.Dr. Kipnis,
A bombshell struck the MS research/treatment sector just this past summer 2015 when it was reported that Dr. Jonathan Kipnis of the University of Virginia had made the totally unexpected discovery that lymphatic vessels drain the brain. Far from being “immunologically privileged” (that is to say without an immune system) the brain is drained by lymphatic vessels which parallel the draining veins. White matter lesions imply as much an immune system DEFENSE of injury to the brain/central nervous system as a pathological process to be suppressed.
This is a major discovery discussed in many prestigious scientific publications including Scientific American. www.scientificamerican.com › ... › Mind Matters.
What does this mean for MS? That the immune system represented by the lymphatic vessels works inside the brain to keep it healthy and suppressing it will likely be harmful. This provides the physical basis for Prof Michal Schwartz’s finding “that immune cells are pivotal for CNS neuroprotection and repair”.
Dr. Kipnis’ discovery of lymphatic vessels in the brain provides the missing factor which reinforces the work of Dr. Maiken Nedergaard, Professor at the University of Rochester, and Co-Director of the Center for Translational Neuromedicine. (She earlier spoke of a "plumbing system" that piggybacks on the brain's blood vessels” without realizing that this “plumbing system” is in fact composed of lymphatic vessels.)
http://www.urmc.rochester.edu/news/stor ... fm?id=3956
And finally we arrive at an understanding that white matter lesions may be less a worry than grey matter atrophy, a shrinking brain which can only mean increased disability.
The entire MS Neurology industry so preoccupied with suppressing lesions on the myelin sheath has been hit in the head.
Already they were aware of “the so called clinicoradiological paradox: Abnormal spots on the MRI often don’t manifest in physical or cognitive symptoms.” See my blog post March 2, 2015 and article dated April 2012. http://www.msdiscovery.org/news/news_sy ... -meets-eye)
In reality MRI scans of white matter lesions are limited indicators of the MS patient’s condition or progression.
The GOOD NEWS is that the progression of grey matter brain atrophy appears to correspond with progression of disability, AND, this atrophy can be measured on an MRI brain scan with a simple ruler. So what are we waiting for?
And the VERY GOOD NEWS is that MSers can help themselves by preventing or reducing this atrophy and theoretically can see the results of their efforts on yearly MRI scans (for example).
In conclusion, every effort must be made enhance fluid circulation throughout the central nervous system, stop any blood reflux, enhance cerebrospinal fluid circulation, stop the relapses and nourish the grey matter as well as the myelin sheath, the earlier the better. Optimal nutrition, supplements, fluid circulation therapies, functional body manipulation, and venoplasty itself if venous stenosis is serious all serve this end.
I am now going to quote directly from a discussion on the ThisisMs.com website triggered by a post by 1 eye on Jan 12, 2016 5:13 p.m. titled “Measuring MS” under General topics.
“http://www.smw.ch/content/smw-2013-13887/
In this document, referred to by Ms. Beal, also called "cheerleader", in at least two posts here (see http://www.thisisms.com/forum/chronic-cerebrospinal-venous-insufficiency-ccsvi-f40/topic27228.html#p238800 ), there is clear evidence for the existence of a set of measurable rates of change in various brain structures in MS, some of which are unique to the MS phenotype.
These measurements give us a clinical non-destructive way of distinguishing these variants of the disease. Various statements have been made about the lack of efficacy of DMDs on the progressive forms of these phenotypes. There may actually be efficacy, especially if atrophy is measured.
If the primary measurable effect of multiple sclerosis is brain atrophy, and if it is measurable using an ordinary ruler, why is it not a standard practise to measure it?
It cannot be true that atrophy is of no consequence. Even if it can be shown that there is no statistical relationship between atrophy and some other currently fashionable clinical measures, surely atrophy itself is the primary undesireable , measurable consequence of the disease. Other details are of less consequence, including broken neurons. The more a brain shrinks, the less possible it is to retrain it.
As an MS patient, there are two related pieces of information that are vital to me.
Across all the MRIs I have had done,
1. What is the current state of my various affected brain structures?
2. What is my rate of atrophy in these affected brain structures?
In addition, the effects of various Disease Modifying therapies on the mathematical derivative, or acceleration of these various rates of atrophy is of extreme interest to MS patients, so they can assess which of these therapies can best slow it down. The required measures can be arrived at using three or more brain MRIs. Each MRI has one data point for the size of each affected atrophic structure. The more MRIs, the more detailed and certain the resulting assessments will be, of atrophy, and of treatment success.”
1 eye is referring to an article in Swiss Medical Weekly dated 21 November, 2013.
Review article: Medical intelligence | Published 21 November 2013, doi:10.4414/smw.2013.13887
Cite this as: Swiss Med Wkly. 2013;143:w13887
Quote:
Brain atrophy: an in-vivo measure of disease activity in multiple sclerosis
Ernst Wilhelm Raduea, Kerstin Bendfeldta, Nicole Mueller-Lenkea, Stefano Magonc, Till Sprengera,b,c
a Medical Image Analysis Centre (MIAC), Basel, Switzerland
b Department of Neurology, University Hospital Basel, Switzerland
c Division of Diagnostic and Interventional Neuroradiology, Department of Radiology, University Hospital Basel, Switzerland
Summary quoted from the article:
Summary Multiple sclerosis (MS) has traditionally been considered to be primarily an inflammatory demyelinating disorder. Nowadays it is recognised as both an inflammatory and a neurodegenerative condition. This recognition is reflected in the development of new disease-modifying therapies that may offer the potential to reduce axon damage, either by inhibiting neurodegeneration or by promoting endogenous repair mechanisms. Since there is only a limited correlation between the clinical features of MS and findings on conventional magnetic resonance imaging (MRI), for the evaluation of such therapies new outcome measures are warranted. Grey matter atrophy occurs in the earliest stages of MS, progresses faster than in healthy individuals, and shows significant correlations with MRI lesion load, cognitive function and measures of physical disability; indeed, brain atrophy is the best predictor of subsequent disability and can be readily measured using MRI. Furthermore, it is becoming clear that currently available therapies differ in their effects on brain atrophy, and this may have important implications for the management of MS. New MRI techniques and advances in software development offer an opportunity to extend brain atrophy measurements beyond research studies to the routine management of MS patients.
Key words: brain atrophy; cerebral cortex; drug treatment; magnetic resonance imaging; multiple sclerosis; thalamus"
The discussion develops on This is MS as follows:
Dr. Geoff Jan 13, 2016
“So, if a simple measurement of brain atrophy is a good measure of MS severity, and if repeated measurements are a good measure of disease progression, and if - as the Swiss study shows - this leads to a direct comparison of the effectiveness of the various DMTs, guess what will happen? Now guess the response from the company that produces the least effective DMT.
Of course, this could be used to compare other things, if used over several years. Diets for example, CCSVI treatment versus DMTs, and there are a lot more.
And the downside? Someone will need to pay for annual MRI scans!”
Geoff
Cheerleader responds on Jan 13, 2016
Thanks for linking this info on the big boy board, 1eye
I began looking at biomarkers for MS progression when Jeff was diagnosed in 2007, after his neuro mentioned that white matter lesions weren't the best correlate for disease progression. I wondered what was?
Over the years, I've followed Dr. Zamboni's research (obviously, as my husband Jeff was the first North American treated for CCSVI) but also the BNAC team in Buffalo, since I met Dr. Zivadinov at the very first CCSVI conference in 2009 in Bologna. BNAC gets funding to image the brain and help pharma understand if/how their drugs are working. And the focus from white matter lesions to gray matter atrophy, specifically the thalamus, began to get more attention in Buffalo.
Almost all of BNAC's pharma funded research is now looking at thalamic atrophy in MS.
This blog post has the links to research, and a link which explains the use of measuring the width of the third ventricle and the thalamus as biomarkers for MS progression. As we all know, disability is not simply a measure of 25 timed walk or EDSS, as cognitive issues can be just as detrimental as physical ones.
http://ccsviinms.blogspot.com/2016/01/t ... ssion.html
The correlation of thalamic atrophy also makes sense in terms of understanding progressive MS---as loss of gray matter is found to continue during the progressive phase of MS. Indeed, gray matter atrophy is the only biomarker that begins with CIS, and ends at the final stages...
Fire away with questions, thoughts, debate, contrary research---but make sure to first check out the blog post, and see if your question is answered there. Will save time/energy here.
http://ccsviinms.blogspot.com/2016/01/t ... ssion.html”
On Jan 13, 2016 Cheerleader continues
But these MS MRI techs are talking about using thalamic atrophy in combination with third ventricle widening in terms of being the best biomarker for MS progression. I think their calculations make sense--it's very specific. Check out the whole paper.
Quote:
Thus, there is a huge need of a methodology suitable to be applied in daily clinical practice in order to estimate GM atrophy in a convenient and comprehensive way. Given the thalamus is the brain structure found to be more consistently implied in MS both in terms of extent of atrophy and in terms of prognostic value, we propose a solution based in this structure. In particular, we propose to compare the extent of thalamus atrophy with the extent of unspecific, global brain atrophy, represented by ventricular enlargement.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4144089/
cheer
On Jan 14, 2016 cheerleader continues
Two researchers who are members of the ISNVD, Zivadinov and Minagar, collaborated on a paper.
It explains thalamic atrophy and MS and summarizes the research-
Quote:
Thalamic pathology, similar to the cortical pathology, appears to be present in MS from very early on, including at the CIS stage and in pediatric MS. In the progressive phase of MS, which is poorly explained by focal inflammatory WM demyelination, cortical and subcortical GM pathology including neuronal and axonal degeneration are the likely substrates for accumulating cognitive and motor dysfunction that characterizes long-standing disease.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589190/
Dr. Minagar is going to be presenting on "MS as a vascular disease" at the ISNVD conference in April.
http://isnvd.org/sites/default/files/IS ... 1-2015.pdf
It is no coincidence that the researchers speaking out on thalamic atrophy and MS are also involved with the ISNVD and looking at MS as a vascular disease.
Why? http://ccsviinms.blogspot.com/2012/01/i ... -know.html
cheer”
ElliotB adds on Jan 15, 2016-
“How To Stop Shrinking Your Brain And Improve Your Thought Process"
http://www.medicaldaily.com/knowledge-b ... ess-302450
Imagine, improved diet, exercise, supplements, and proper sleep can all help your brain - what a novel idea!”
On January 16, 2016 cheer rejoins
“Yup! Great link, Elliot. So much we can do to maintain gray matter.
Here was my list of what to do on "Gray Matters" Written and put on line in 2012: Links to research included!
https://www.facebook.com/notes/10151031434857211/
Quote:
1. eat fish or take an omega 3 supplement
2. exercise. walk if you can, swim, practice seated yoga, dance, bike, move.
3. discover a new interest-- a foreign language, knitting, oil painting, floral arranging, cooking, juggling.
4. get vitamin D from sun and/or supplement
5. meditate
6. get plenty of good sleep, and take naps.
7. listen to music...even better, sing along or play an instrument.
8. read a book or join a book club
9. eat Indian food, or take a curcumin supplement. If curcumin is contraindicated for you, you can skip this one
10. hug often. A pet, a grandkid, a spouse, a tree, a friend--yourself
“cheer” goes on to explain to 1 eye
Everything I recommended to improve gray matter health has published reseearch behind it.
I will copy over all the lnks, because I know you don't like going to other pages, like the one Iinked https://www.facebook.com/notes/10151031434857211/, but I don't make it up. I merely compile research...never claim to be anything more than an interested layperson who has been looking at the connection of MS to gray matter atrophy for a few years now....
1. eat fish or take an omega 3 supplement
http://www.ncbi.nlm.nih.gov/pubmed/17574755
2. exercise. walk if you can, swim, practice seated yoga, dance, bike, move.
http://www.ncbi.nlm.nih.gov/pubmed/19560443
3. discover a new interest-- a foreign language, knitting, oil painting, floral arranging, cooking, juggling.
http://journals.plos.org/plosone/articl ... ne.0002669
4. get vitamin D from sun and/or supplement
http://yaledailynews.com/blog/2015/11/1 ... -patients/
5. meditate
http://newsroom.ucla.edu/releases/how-t ... rain-91273
6. get plenty of good sleep, and take naps
http://www.ncbi.nlm.nih.gov/pubmed/24346259
7. listen to music...even better, sing along or play an instrument.
http://www.medicalnewstoday.com/articles/246675.php
8. read a book or join a book club
http://www.ncbi.nlm.nih.gov/pubmed/25203270
9. eat Indian food, or take a curcumin supplement. If curcumin is contraindicated for you, you can skip this one
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527619/
10. hug often. A pet, a grandkid, a spouse, a tree, a friend--yourself
http://opinionator.blogs.nytimes.com/20 ... love/?_r=0
What if there is no "fix"? What if the "cure mentality" keeps us from addressing the things we can change today?
http://ccsviinms.blogspot.com/2014/06/t ... ality.html
Preserving and enhancing gray matter is real. Neuroplasticity is real. It may well be "the fix." Read Norman Doidge's new book, The Brain's Way of Healing...be encouraged and inspired. http://www.normandoidge.com/?page_id=1042 Outlive that solar contract!!! Outlive the fix!
xoxox,”
cheer
On Jan 17 1eye refers to:
Proposed method for measuring dRA, or delta Rate of Atrophy:
http://sullivanweb.me/pdfdocs/atrophy-3.pdf
This link refers to the following excellent article. I’ll quote it even though I don’t know the author’s identity. 1eye explains the calculations thereafter.
“I do not think we are keeping complete records of atrophy, which can describe the progress of MS disease. We can also use these records to demonstrate treatment success.
I propose an accurate measurement of brain atrophy in an area of white or grey matter known to be subject to it. A location is measured using bone as a reference point, say the top of the skull, or the point of a tooth. This reference is used to measure the size of the organ of interest, at a given MRI slice. As much as possible a reproducible location is used to make a size measurement.
The series of MRI measurements are repeated at intervals separated by at least a year. One MRI measurement gives the current size at a given location, of the given organ. For example the size might be measured each time to 0.5 mm accuracy.
The reason for making series measurements at the same latitude and longitude of a brain, is to assess any changes in size. That will tell us whether the organ has grown, shrunk, or stayed the same size.
The first measurement tells size alone. The second, in combination with the first, should reveal the current rate of atrophy, at the chosen location, expressed in millimeters per day. The third measurement, when compared with either of the first two, would also show a rate of atrophy.
Comparing MRI-1 and MRI-2 you get the Rate of Atrophy (RA) over the time frame t2 minus t1. Call this measured rate RAa. Comparing MRI-2 and MRI-3 you get the RA over the second interval t3 minus t2. Call this measurement RAb.
You can also, by comparing MRI-3 with MRI-1, confirm the RA at t3. Call this rate RAc.
These measurements give the organ’s size changes over the interval between the first two MRIs as well as the size changes between the second two MRIs. Using the overall time between first and last measurements will produce a measurement of the organ’s size changes over the interval between them.
Using calculated values in the three measurements you can produce a table:
MRI number organ size (mm) time of MRI RA (mm/day)
1 xx.xx DDMMYY hh:mm:ss 0.0 at t1
2 yy.yy DDMMYY hh:mm:ss RAa at t2
3 zz.zz DDMMYY hh:mm:ss RAb at t3
You can compare the atrophy rates at t2 and t3 to produce a rate of change of atrophy rates between the last two MRIs, in millimeters per day per month, for instance. The way to calculate this is to subtract RAb from RAa, producing delta-RA, or dRA. This will be positive if the organ’s atrophy rate has worsened, 0 if there was no change, and negative if there has been a slowdown of the rate of atrophy.
The overall measurement from t1 to t3 is a rate of atrophy that is more averaged, over the entire three years.
dRA is the more useful measure, showing change from one year to the next.”
On Jan 20, 2016 1 eye wrote
So here's a picture:
http://sullivanweb.me/pdfdocs/atrophy-4.pdf
This hypothetical patient shows -8.3 um atrophy per day in the first interval, and the atrophy changes such that the first interval's atrophy is partly reversed at a dRA of +0.85 um/day/month.
This measurement represents partial regrowth of brain matter at the third MRI at t3, which had previously deteriorated by the time of the second MRI at t2.
OK, so I did the unthinkable: I bumped and re-posted on my own thread. But I just wanted to say: the result of this measurement is a direct quantitative measurement, which at least is an analog to, and at best measures MS directly, puts a number to a patient's either improvement or worsening. Healthy controls should show dRA (delta Rate of Atrophy) = 0.
This measurement verifies with counting lesions, black holes, EDSS, and any other measure of MS. It can be done as a sanity check to every purported treatment improvement. A good treatment either reverses, slows down, or stops the disease. This one measurement can put a number on any of those changes, or show very clearly that there has been no change. Qualitative descriptions of these conditions is not good enough, when we are using machines that cost upwards of $30 million, with modern imaging, storage, and computing power.
If their physician won't do it, patients can actually do that same measurement for themselves, using whatever measuring tools (a ruler of some kind) are at their disposal. All you need are three time-separated MRIs. These are available: in most cases, the patient owns them.
See also http://sullivanweb.me/pdfdocs/atrophy-3.pdf
and http://sullivanweb.me/pdfdocs/atrophy-4.pdf
The Ottawa Hospital has some of my MRIs. In the one I had in 1997 the radiologist reported an atrophic corpus callosum. Along with the one I had in 1996, that forms a complete baseline RA measurement. I would like to see the dRA at my corpus callosum from every MRI I have had since (there have been many).
In the same discussion I eye also explains the calculations as being simple arithmetic. Excellent work.
I will need to revise my main paper in keeping with the brain atrophy issue.
I believe it perfectly reasonable to insist on an MRI of one’s brain grey matter/thalamus, and then embark on the healing programs outlined in my site – see 5 Steps to MS Health for instance, or Matt Embry’s program, and then continue with periodic MRI’s that monitor the brain’s condition. At least now there exists a physical, material basis for monitoring one’s MS progression, and also the possibility of being encouraged to continue a program that may appear tiresome.
UPDATE JANUARY 31, 2016
1 eye has just answered my query about the identity of the wonderful sullivanweb articles. He has identified himself as CHRIS SULLIVAN. He is Canadian and a well informed reliable contributor to the Thisisms.com site.
1 eye Jan 24, 2016
Sorry. You cannot find that link to sullivanweb.me anywhere (that I know of) except right here in this thread. There might be something close on my computer. Chris Sullivan is apparently the alter ego of 1eye, when he is at home. It's not really for publication anywhere, just a post to TiMS that ran astray; however the picture shows what the dRA is, and how you might use it to assess how one is doing after some kind of intervention. Atrophy is either worse, the same, or better, and dRA says how much, if it's not 0. If it is, you are young and healthy.
The clue is in the units: the hypothetical patient is getting better (just because of the sign), and the speed of the improvement is increasing, by as much as 0.85 um per day, every month since the intervention.
P.S. Sullivan is Gaelic for "one-eye".
Tags: Multiple Sclerosis treatment, MRI, Grey matter atrophy, Thalamus,.Dr. Kipnis,
RSS Feed