Theoretical Immunology

[NHE]

1. Why is it only that the myelin (white matter) is inflamed and not other tissue such as the grey matter?

Gray matter is damaged in MS.

Gray matter damage in brain of MS patients linked to cognitive, physical deficit http://www.thisisms.com/article-7-thread-0-0.html

In addition, there have been multiple posts discussing gray matter damage.

Just one paper of many...

Gray- and white-matter changes 1 year after first clinical episode of multiple sclerosis: MR imaging. Radiology. 2010 Nov;257(2):448-54.

RESULTS: After 1 year, multiple sclerosis (MS) was diagnosed in 33 (97%) of 34 patients with CIS. Longitudinal volumetric analysis revealed a significant (P < .001) reduction in global GM volume. The voxel-based morphometry analysis showed the development of regional GM atrophy involving several cortical and subcortical regions in both hemispheres (P < .05). No significant longitudinal change in global or regional WM fractional anisotropy was otherwise observed.

CONCLUSION: WM damage was detectable early and involved most fiber tracts in patients with MS, but it did not worsen significantly during the 1st year after clinical onset. In contrast, GM damage was not detectable at the time of clinical onset, but a significant decrease in cortical and deep GM volume was observed at 1 year.

NHE

[bluesky63]

To the summary/hypothesis, I might add that some people may be more genetically susceptible. MS can be associated with families who have a high number of members with other issues, many of which could be explained by undiagnosed malabsorption issues, inherited mitochondrial syndromes of varying expression, collagen defects, and so on.

The interplay of these physical conditions with lifestyle and medical management would result in many different scenarios!

Adding to the sugar story, here is an article on the different behavior of fructose and glucose in the brain (should I label it giant url?):

New study confirms fructose affects your brain very differently than glucose
<shortened url>

This is the abstract that dramatic article seemed to originally stem from:

http://onlinelibrary.wiley.com/doi/10.1 ... x/abstract

[CVfactor]

1. Why is it only that the myelin (white matter) is inflamed and not other tissue such as the grey matter?

Gray matter is damaged in MS.

Gray matter damage in brain of MS patients linked to cognitive, physical deficit http://www.thisisms.com/article-7-thread-0-0.html

In addition, there have been multiple posts discussing gray matter damage.

Just one paper of many...

Gray- and white-matter changes 1 year after first clinical episode of multiple sclerosis: MR imaging. Radiology. 2010 Nov;257(2):448-54.

RESULTS: After 1 year, multiple sclerosis (MS) was diagnosed in 33 (97%) of 34 patients with CIS. Longitudinal volumetric analysis revealed a significant (P < .001) reduction in global GM volume. The voxel-based morphometry analysis showed the development of regional GM atrophy involving several cortical and subcortical regions in both hemispheres (P < .05). No significant longitudinal change in global or regional WM fractional anisotropy was otherwise observed.

CONCLUSION: WM damage was detectable early and involved most fiber tracts in patients with MS, but it did not worsen significantly during the 1st year after clinical onset. In contrast, GM damage was not detectable at the time of clinical onset, but a significant decrease in cortical and deep GM volume was observed at 1 year.

NHE

O.K. I think Leonard should change his hypotheses to include damage to all cell types of the central nervous system.

This would include Ependymal cells that are responsible for production of cerebral spinal fluid. Thus we can conclude his hypotheses should show a dysfunction of CSF production in people wit MS.

[Leonard]

...there is the distinct possibility that what we call Multiple Sclerosis isn't really one disease at all, but rather a collection of similar diseases that share symptomatic and diagnostic profiles.
from: http://www.wheelchairkamikaze.com/2011/ ... rbole.html

In my view, mid-age onset MS has, in addition to the venous obstruction which is pre-congenital and can be opened by angioplasty, a lot in common with diabetes2. Here, you could say Multiple Sclerosis is a combination of different conditions.

1. The remarkable features of MS seem diabetes2 related:
2nd peak diabetes at mid-age and the Vitamin D relation explained by vein/RBC hardening:
http://www.thisisms.com/ftopict-15188.html posting 30 Jan 6:11

2. The symptoms of diabetes and MS show a remarkable similarity:
http://diabetes.niddk.nih.gov/dm/pubs/neuropathies/
http://care.diabetesjournals.org/conten ... 984.1.full

3. MS, iron, diabetes and myeline damage
MS, iron deposits and myeline change long known
for iron build up, diabetes and myeline change: <shortened url>

4. The diabetes drug helps MS:
http://findarticles.com/p/articles/mi_m ... _97390042/
http://www.ivanhoe.com/channels/p_chann ... ryid=11042

5. The prevalance of diabetes in MS

6. The history of diabetes that neurologists had to give up the disease after endocrinologists proved that it was not neurological:
http://www.ccsvifoundation.org/faq.php
http://www.scientificamerican.com/artic ... utube-cure see comment 6 from andissue

7. The discussion in 1980s about MS and diabetes being the same disease.
The discussion disappeared in the background as ccsvi was not known at the time. But what after Zamboni discovered ccsvi and patients are liberated from ccsvi, isn't there a need to review MS or whatever remains after liberation as a "neurological" disease?

Besides neurologists, vascular specialists and interventional radiologists, this review would need to involve endocrinologists.

[Leonard]

1. Why is it only that the myelin (white matter) is inflamed and not other tissue such as the grey matter?

Gray matter is damaged in MS.

Gray matter damage in brain of MS patients linked to cognitive, physical deficit http://www.thisisms.com/article-7-thread-0-0.html

In addition, there have been multiple posts discussing gray matter damage.

Just one paper of many...

Gray- and white-matter changes 1 year after first clinical episode of multiple sclerosis: MR imaging. Radiology. 2010 Nov;257(2):448-54.

RESULTS: After 1 year, multiple sclerosis (MS) was diagnosed in 33 (97%) of 34 patients with CIS. Longitudinal volumetric analysis revealed a significant (P < .001) reduction in global GM volume. The voxel-based morphometry analysis showed the development of regional GM atrophy involving several cortical and subcortical regions in both hemispheres (P < .05). No significant longitudinal change in global or regional WM fractional anisotropy was otherwise observed.

CONCLUSION: WM damage was detectable early and involved most fiber tracts in patients with MS, but it did not worsen significantly during the 1st year after clinical onset. In contrast, GM damage was not detectable at the time of clinical onset, but a significant decrease in cortical and deep GM volume was observed at 1 year.

NHE

O.K. I think Leonard should change his hypotheses to include damage to all cell types of the central nervous system.

This would include Ependymal cells that are responsible for production of cerebral spinal fluid. Thus we can conclude his hypotheses should show a dysfunction of CSF production in people wit MS.

please propose me some text.

in a posting above, your comment on the need for the presence of a virus (Bar Eppstein??) to start the process is interesting. may be you could elaborate on that a bit as well.

then your comment on an other thread on interferon gamma is also interesting.
is there any link you could imagine with calcification/hardening of veins and RBCs?
if so, is interferon gamma prescribed by endocrinologists?
I was looking at the conference programs of endocrinologists yesterday ans found that interferons are a normal medication in their tool set too.

[CVfactor]

Some researchers believe that cetain pathogen peptides have similar structure to myelin basic protein which may be the reason why MBP is a target in people with MS.

http://www.cell.com/immunity/abstract/S ... %2900112-5

Interferon-gamma is a pro-inflamitory cytokine (chemical signal) produced by T-helper cells to initiate an inflamitory immune response.

Interferon-beta is a class of MS disease modifying drugs.

Although they have similiar names, they are not related. Interferon-gamma would be a counter-productive if used in MS so it will never be made into a drug.

More information is found here:

http://www.thisisms.com/ftopict-15479.html

[Leonard]

A beautiful presentation from Dr. Simka about what we know and what we don't know about MS and ccsvi: <shortened url>

There is a third dimension missing here. And that is the dimension of nutrition of the cells / glucose deficit / diabetes link etc, in short the story of this thread.

Yesterday I googled a bit on diabetes multiple sclerosis and was almost blown away from the screen by the response. There is so much more than what I found from the same search just one month ago. Some of the links point to articles that are really very interesting and relevant indeed.

It seems likely that there is something here that goes beyond MS and ccsvi, a 3rd dimension of cellular biology and feeding, that needs to be factored in.

[leeyn]

I believe six pediatric MS centers have been established across the US. I suspect this has happened because younger and younger children are consuming diets of more items that readily convert to glucose......

[Leonard]

This introduces the nutrition (oxygen/glucose) dimension in the ccsvi debate.


Quote from http://www.thisisms.com/ftopic-15590-60.html

Press Release of March 15, 2011

ISNVD Annual Meeting

ISNVD is the International Society for Neurovascular Disease,

at present highly committed to the study of CCSVI


Bologna, March 14 and 15, 2011


Many of the issues which are still open on the relationship between CCSVI and MS found an answer at the ISNVD (International Society for Neurovascular Disease) Annual Meeting. The Society, chaired by Prof. Paolo Zamboni, held its meeting in Bologna (Italy) on March 14-15, 2011 under the High Patronage of the President of the Italian Republic.

The Meeting – attended by registered physicians, researchers and accredited journalists – was preceded by a preliminary meeting of the International Scientific Committee on Sunday March 13. It was organized in the form of a Consensus Conference with the purpose of defining minimum starting points in the approach to the investigated diseases.

...

ROLE OF OXYGENATION AND TISSUE DRAINAGE

Among the questions that were answered at the Meeting was also a fundamental one which relates to the observation made by Bruce Trapp from Cleveland (one of the most eminent MS researchers) according to whom nerve cell damage and death are due to an axonal asphyxial phenomenon which has not been yet completely clarified.

...

unquote

Asphyxia is caused by a reduction in the supply of blood or oxygen.
When searching, I find closely related terms: hypoxia and ischemia.

Hypoxia is a more general term denoting a shortage of oxygen, usually a result of lack of oxygen in the air being breathed.

Ischemia is an absolute or relative shortage of the blood supply to an organ, i.e. a shortage of oxygen, glucose and other blood-borne fuels. A relative shortage means the mismatch of blood supply (oxygen/fuel delivery) and blood request for adequate metabolism of tissue. Ischemia results in tissue damage because of a lack of oxygen and nutrients [1]. Ultimately, this can cause severe damage because of the potential for a build-up of metabolic wastes.

From Wikipedia, .. cerebral hypoxia-ischaemie there was a period of time before brain cells started to die.

So again, just like what happened in the 1980's when diabetes2 was carried over from the neurology to the endocrinology, with the introduction of this nutrition dimension in the MS/ccsvi debate, has the time come to look at MS from the angle of the endocrinologists?

[Leonard]

Just to keep this thread as complete as possible, this is a copy of an earlier posting on:
http://www.thisisms.com/ftopic-7708-45.html

From dr. Haacke's paper:
Back in the 1980s, Swank et al. found that past the age of 40 years, MS patients had markedly reduced blood flow compared with normal individuals [26].
http://www.expert-reviews.com/doi/pdf/1 ... ern.10.174
The same text is now proliferating through other channels e.g. http://www.medscape.com/viewarticle/734517_3

But the actual publication suggests something more than what is mentioned in dr. Haacke's paper, namely that it is not just the blood flow, but also the RBC delivery: Swank RL, Roth JG, Woody DC Jr. Cerebral blood flow and red cell delivery in normal subjects and in multiple sclerosis. Neurol. Res. 5(1), 37–59 (1983).
In the patients with multiple sclerosis there occurred a progressive generalized decrease in CBF and in RCD with age which was significantly greater than observed in normal subjects. The rate of decrease in CBF and RCD correlated directly with the rate of progress of the disease. (RCD = Red Cell Delivery)
http://www.ncbi.nlm.nih.gov/pubmed/6140655

This ties in with an earlier posting on TIMS on the increased ATP level in MS patients (300%). The high level is probably best explained by signallers in the body calling out loudly for help (Endothelin1?) and the fact that the RBC (Red Blood Cells) do not release the ATP, at least not enough.

This may well be related to the hardening/calcification starting at mid age (but not necessarily exclusively). Traditionally, this hardening was understood as a hardening of the arteries, we know now that also the veins are subject to hardening. But I found several references that, besides the hardening of the vessel walls, also the release of the nutrition (= the release of ATP from the RBC) is now understood to be an issue.

In this same context of hardening/calcification, this is potentially of greatest importance: http://en.wikipedia.org/wiki/Ischemic_cascade
4.The ion pumps can no longer transport calcium out of the cell, and intracellular calcium levels get too high.
Hence the inflammation of the BBB may be a very important factor adding further to the hardening/calcification of the BBB and causing a vicious circle, making nutrition even more difficult etc.

I read the material on ATP on Wikipedia. The ATP is the main supplier of energy to the body. It is a phosphor something that contains the mixture of the glucose with the oxygen. In fact, it is not just the glucose or oxygen that passes through the veins to the cells; that is done through a more sophisticated mechanism involving the ATP and is called the "aerobic glycolysis". My attention that that was drawn on this thread (which shows the value of these fora) http://www.thisisms.com/ftopic-15188-da ... sc-45.html

Just to demonstrate the scale of the issue which gives a feeling for the size of the problem: the total volume of ATP that is recycled every day (that is ATP taking on glucose and oxygen and releasing that in the destined cells) is as big as the total mass of the body. You can see that if there is a problem with the RBC release of ATP, the body will have a problem. If in addition to the locking of the ATP in the RBC, you already have a low flow because of the stenoses, you have a serious problem. The concept that is described here is no different from my hypothesis on the above thread.

Last month, I have done a lot of searching on ATP, glucose and insulin. And I believe that I can tell from the search engine (if you understand how Google works), that people - probably including many professionals- are massively searching on this topic. And there are some names, mainly in the US, who are in fact on top of this.

In this same context of ATP, this hypothesis is interesting
http://www.pnas.org/content/96/2/329.long
It concludes quote … greatly expanding the list of tangible hypotheses for the etiology and treatment of non-insulin-dependent diabetes mellitus unquote to which I would add … and for the etiology and treatment of MS.

[Leonard]

This is also a copy of an earlier posting on the ccsvi chapter of this forum:

The bood flow is very important, but we should not entirely forget the capacity of the RBCs to carry the suppy of energy, that is for making/recycling the ATP and releasing the ATP.

On Wikipedia, the 'Ischemic cascade' is defined as a series of biochemical reactions that are initiated in the brain short time after inadequate blood supply, typically due to stroke. The series of events that happens then shows some similarities with MS. This makes me wonder whether MS is perhaps something like an Ischemic cascade but then on the long-term, that is not due to immediate inadequacy of blood supply, but a real slow process of under-nourished cells that eventually start to die? This would suggest a nutrition concept of the issue.

On this nutrition side, these articles are of interest.

The first article was published in May 2007 and was republished on 29 December 2010 reads: A glucosamine-like dietary supplement has been found to suppress the damaging autoimmune response seen in multiple sclerosis....
Now carefully watch the wording used: the use of the word 'suppress' is an indication of how people in the research field think about the concept of issue, it is starting from the presumption that MS is an immune disease that needs to be suppressed.
But perhaps they should have looked at it from the other side: that is to say ... the supplement has been found to calm down the immune system..
where the nutrition or better lack thereof causes a cascade of effects that eventually leads to MS.
http://www.health-caree.com/glucosamine ... betes.html

The second article is a bit more of the same: again reasoning from the side of anti-inflammatory effects. But the same article talks ... of the drugs' effect on the body's response to insulin. Here I ask myself: is the way to look at the problem from the side of the anti-inflammatory effects the right way? Just like with diabetes2, shouldn't we look from the other side, that is to say: to calm down the immune system and inflammation by better feeding of the cells..
Then you get exactly the debate that was held in the 80's when endocrinologists proved that diabetes was not an auto-immune disease. And as a result the entire field was carried over from the neurology to the endocrinology.
http://www.sciencedaily.com/releases/20 ... 171809.htm

I compare the picture that emerges here a bit with a cookie factory producing nice cakes with a chocolate topping. The production belt fails somewhere in the cascade of steps. At the end of the belt, the alarm bell starts ringing. And what does the operator do? He throws his jacket over the alarm bell and rests back in his chair. And the chain just rumbles on ..

[Leonard]

I have searched a bit on ion pump calcium transport and intracellular calcium. It shows that calcium channel blockers are very common, for instance for use against hypertension.

For MS, this study is very interesting:
http://www.ncbi.nlm.nih.gov/pubmed/15296830
The article confirms that the influx of calcium via the voltage gate plays an important role in the developments of neurological disability and damage to the white matter for ... MS!!

I am really curious whether anything has been done after 2004 on this line of thought; or conversely whether things have just disappeared on the shelf (and if so why?)

[Cece]

Leonard, keep at it, you are doing great. Lots to read through and think about here.

[jimmylegs]

magnesium is your dietary/supplemental calcium channel blocking option

[1hunter]

should we avoid calcium suppliments? I'm lost here