MS begins in the gray matter

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frodo
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MS begins in the gray matter

Post by frodo »

It seems that in CSF collected after the CIS of several persons, all the proteins were pointing to gray matter degeneration instead of the white matter myelin.

http://www.nj.com/news/index.ssf/2013/0 ... ieved.html

And besides, these proteins can be used as biomarkers to diagnose MS after the CIS but before the second attack.

http://www.msdiscovery.org/news/new_fin ... ray-matter
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Re: MS begins in the gray matter

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Degeneration leading to grey matter atrophy?
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frodo
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Re: MS begins in the gray matter

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1eye wrote:Degeneration leading to grey matter atrophy?
It seems so. I have just found the paper

http://journals.plos.org/plosone/articl ... ne.0066117
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Re: MS begins in the gray matter

Post by Leonard »

Pols One is great; there is so much to say in favour of open literature on the Internet. I think it will take over from the established channels.

On the issue itself: there is HERV activation with the herpes virus. Cells are in crisis and will shed cytokines, chemokines, proteins etc. The immune system reacts. You see CIS. The proteins associate with the grey matter, not the myelin.

RR follows. It is VZV specific. T-cell immunity is partly surpressed by VZV. With toxins, the immune reaction causes white matter lesions. Over time, the immune system learns and gets better control. That is why RR wanes with time.

Later on HERV/EBV B cell growth will cause huge oxidative stress, mitochondrial failure and failure to supply enough energy for the ion pump. Motor functions are impaired. The B cell problem stops around 60. That is also why there are no new reported cases of MS after 60.
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Re: MS begins in the gray matter

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Thanks for the paper, Frodo. Great find. Here's the link again...in case people would like to read it. 8O http://journals.plos.org/plosone/articl ... ne.0066117
Another one to add to the stack showing how gray matter involvement begins even before an MS diagnosis. Ironically, the researchers set out to disprove gray matter involvement, by using CSF samples of those not yet diagnosed (CIS), and compared them to RRMS samples and healthy controls. They found 20 CNS proteins detected in the CSF that showed significant differences between the 3 groups. Turned out the axonal/gray matter associated proteins were degraded in CIS more than the myelin proteins. Surprise!!!!
There were a total of 20 such proteins. Nine were significantly increased in first-attack CIS MS compared to both groups. The most striking increase was in soluble Nogo receptor. Five proteins were significantly decreased in first-attack CIS MS compared to both other groups. Another six proteins were significantly increased in the first-attack CIS MS group compared to established RR-MS, but significantly decreased compared to levels in control CSF. At least 15 of these 20 proteins (75%) affect synapse, axon, and neuron functioning (gray matter associated), as opposed to myelin (white matter). Myelin proteins were detected in both established RR-MS and first-attack MS including myelin oligodendrocyte glycoprotein, myelin-associated glycoprotein, and proteolipid protein. They did not exhibit quantifiable differences in abundance. Neuronal related proteins, such as amyloid precursor protein, and neuronal adhesion molecules, such as NCAM, were also found among the 20 proteins. In another set of first-attack MS CSF samples that were previously profiled by offline 2D-LC-MS/MS (without applying immunodepletion due to sample size limitations), all the above 20 CNS-specific proteins were detected at significantly higher concentrations than the myelin proteins.
There is an increasing literature on the importance of gray matter, neuronal and axonal involvement in MS, even at very early time-points [17]. Our findings support this, and indicate that axonal, neuronal and synaptic involvement may be required for the initial presentation of MS. It is interesting in this disease, which is characterized by demyelination as it progresses, that gray matter components may be diagnostically more useful than myelin components at the earliest stages
Leonard...
do you even read papers before you start commenting??? Seriously.
There is NOTHING in the paper Frodo linked above on herpes. Nothing on B cells. Nada. Niente. Nulla.
It's a study on brain protein degredation and CSF levels.
Also, I know three people who were diagnosed with MS after 60. One person was 65.
What's with you and your "facts"??? Please provide links to stuff you claim.
5% of people dx w/ MS are over 50.
http://www.everydayhealth.com/multiple- ... er-in-life
cheer
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Re: MS begins in the gray matter

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frodo wrote:
1eye wrote:Degeneration leading to grey matter atrophy?
It seems so. I have just found the paper

http://journals.plos.org/plosone/articl ... ne.0066117
Yup. And in the references:
4. Calabrese M, Rinaldi F, Mattisi I, Bernardi V, Favaretto A, et al. (2011) The predictive value of gray matter atrophy in clinically isolated syndromes.
Neurology 77: 257–263.
This is pretty revealing. As they speculate, grey matter atrophy is probably the first clinically measurable symptom in Clinically Isolated Syndrome. It can be tracked over the entire duration of the disease, which is often for the entire remaining life of the patient. The third of three MRIs after that time will indicate whether he rate has changed, and for better or worse.
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Leonard
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Re: MS begins in the gray matter

Post by Leonard »

hi cheer,

you are right, my wife says the same thing. She often tells me: you don't read the papers, you just scan them.
That is probably true for most of them. But some I read, sometimes 2 times, or even three times, word by word...
They have to fit in my picture, in my believe, they have to fit a wider concept, they have to complement or add...

You may think this is all wrong, and may be you have a point.
Medical professionals don't work like that, it all has to be very precise..
I am an engineer by training, I have a 35 year career behind me, the last 20 years in high level policy making, before as a systems engineer and as a systems planner and investment/cost controller.
I work different than medical professionals; in my entire working life I always tried to keep an overview, to see the landscape (and -yes- the detail when it matters).....

The matter MS is complicated and we should - if we are ever to surface - make sure that we don't get swamped in the detail, that we don't get derailed by false believes or flawed concepts.

If you look at epidemiological evidence, both VZV and EBV play a role in MS.
There can be no argument about that; epidemiological studies don't lie if they are well conducted.
I found a handful of these studies on the Internet. Here are some on VZV:

http://www.ncbi.nlm.nih.gov/pubmed/24635924

http://www.ncbi.nlm.nih.gov/pubmed/18306233

http://jid.oxfordjournals.org/content/204/2/177.full

http://www.nature.com/nrneurol/journal/ ... o0798.html

http://www.hindawi.com/journals/msi/2011/214763/

https://en.wikipedia.org/wiki/Pathophys ... _sclerosis

I can only repeat what I said above, the evidence is there, it may be an inconvenient truth for many but the viral dimension is undeniable:

RR is VZV specific. T-cell immunity is partly surpressed by VZV. With toxins, the immune reaction causes white matter lesions. Over time, the immune system learns and gets better control. That is why RR wanes with time.

Later on HERV/EBV B cell growth will cause huge oxidative stress, mitochondrial failure and failure to supply enough energy for the ion pump. Motor functions are impaired. The B cell problem stops around 60. That is also why there are no new reported cases of MS after 60.

Forget about the detail i.e, that some may be diagnosed after 60. Just look at the main stream..

I think the ISNVD should look into VZV as a major cause of MS.
But now I better shut up because you probably get bored with me .... :sad:

regards, Leo
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Re: MS begins in the gray matter

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OK....reading your papers. Thanks, Leonard.
1. is on relapses. The original paper we're discussing is on gray matter involvement before relapses or immune activation.
2. is on relapses. see above
3. is a very good review, linking VZV and latent VZV to autoimmune reaction in MS.
4. is on relapses
5. A review, but no CSF, nothing before relapses.
In our studies, findings of DNA from these two viruses in MS patients were not different from controls; also, particularly during exacerbations of MS the results were not different from those obtained during remission.
6. is wikipedia.
All of the above papers linked above are in RRMS, whereas the gray matter paper we are discussing shows axonal loss prior to an MS diagnosis, during CIS.
http://journals.plos.org/plosone/articl ... ne.0066117
Actual neurodegeneration prior to an MS diagnosis, which continues on into progressive MS


I would like to suggest, as I have many years now, that viruses are one of many endothelial disrupters, which slow cerebral bloodflow, lead to hypoperfusion and create neurodegeneration. The key is learning which endothelial disrupters are affecting the individual. Cpn, EBV, low vitamin D, smoking, lack of exercise, stress, obesity, misaligned cervical spine, microbiome, disrupted sleep....are all factors. Big picture.
Vasculopathies caused by varicella zoster virus (VZV) are indicative of a productive virus infection in cerebral arteries after either reactivation of VZV (shingles) or primary infection (chickenpox). VZV vasculopathy can cause ischaemic infarction of the brain and spinal cord, as well as aneurysm, subarachnoid and cerebral haemorrhage, carotid dissection, and, rarely, peripheral arterial disease.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2814602/
The ISNVD is looking at this.
The study found that CCSVI risk factors occurred more frequently in those with a history of mononucleosis, i.e. infected with Epstein-Barr virus; those with irritable bowel syndrome; and those who smoke or have a history of smoking.
“All three are confirmed risk factors for MS,” says Bianca Weinstock-Guttman, second author on the study and UB professor of neurology. The results showed that individuals with CCSVI were 2.7 times more likely than individuals without CCSVI to have infectious mononucleosis, 3.9 times more likely to have irritable bowel syndrome and 1.98 times more likely to have a history of smoking.
“Our finding that a risk factor that is highly significant for MS—Epstein-Barr virus, indicated by a history of infectious mononucleosis—is strongly associated with CCSVI, is important,” says Zivadinov.
http://www.buffalo.edu/ubreporter/archi ... sk_factors
cheer
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Re: MS begins in the gray matter

Post by 1eye »

While I have been looking at pictures both big and small, I have noticed a study somebody posted about Japanese MS patients' microbiota. They include about 1000 species of bacteria, and Japanese pwMS have more of 1 species, and less of 2 other species. At the same time some people in a French trial of biotin 300mg have done well. I do not think it is a coincidence that biotin is produced by a couple of gut bacteria species. I think there may be some interaction with a viral pathogen like EBV and/or some protein produced by gut bacteria which causes the gradual destruction displayed in MS.

We may be dealing with more than one type of pathogen, both viral and bacterial, for instance. This type of interaction could as easily happen during CIS, and cause neurodegeneration and/or endothelial damage. We don't know so much more than we do.
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Re: MS begins in the gray matter

Post by frodo »

Just to keep similar things together, a couple of new articles about the same subject has just been published.

Widespread synaptic loss in multiple sclerosis

http://brain.oxfordjournals.org/content/139/1/2

And a second one:

Neurodegeneration Triggers Peripheral Immune Cell Recruitment into the Forebrain

http://www.jneurosci.org/content/36/4/1410.short

(Edited to add the second article)
Last edited by frodo on Tue Feb 02, 2016 9:47 am, edited 2 times in total.
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Leonard
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Re: MS begins in the gray matter

Post by Leonard »

thank you frodo for the link. very appropriate.

thank you cheer for the link to the Maria Nagel article. if you read this, read it in a wide sense, between the lines, try look beyond the immediate horizon, and you see MS in many ways: the VZV vasculopathy images, the lesion in the grey - white matter junction, the eyes nerve infection, the inflammation of the meningeal system, the connection with the pharyngeal system, etc.

The current understanding of MS (which is not really an understanding) developed from an other side, namely the clinical observations in the 50's en 60's. Even today doctors look there. But have you ever asked yourself how different that could have been if the understanding of MS had developed from what underlies this Maria Nagel article?

For sure, it would have been very different and much closer to reality...
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Re: MS begins in the gray matter

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Vasculitis (plural: vasculitides)[1] is a group of disorders that destroy blood vessels by inflammation.[2] Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis.[3] Vasculitis is primarily caused by leukocyte migration and resultant damage.

Although both occur in vasculitis, inflammation of veins (phlebitis) or arteries (arteritis) on their own are separate entities. -Wikipedia


My mother died of vasculitis.

What is causing degeneration of grey matter from CIS and before, to EDSS 9?

Could it be some process that is triggered by VZV? Chicken pox usually hits kids, and most don’t reactivate until adultood, when chicken pox acts completely differently, so it’s called shingles.

Both phlebitis and arteritis, forms of vasculitis, (note, we are not discussing joint pain) are diseases of the blood vessels. The endothelium of veins can be distorted into stenosis. Often veins are already distorted at birth by genes, or later by traumatic obstructions. This distortion is a hallmark of CCSVI. How often is it found in MS?

The pressure is low, the vessel walls are soft, because most of the time they don’t need to be hard. In fact, if the venous system were designed as well as the arterial one, veins would not be very changeable by genetic susceptibility, trauma, environment, or infection. Perhaps two hearts, one to pump out and to the lungs, the other to bring venous blood back in, and from the lungs.

If it is vascular and venous-only, why isn’t it a problem in the lungs?

In lungs, venous vessels are as abundant as their arterial counterparts. If the lung blood vessels were as diseased as the brain and spine is in MS, it would be a serious lung disease. However, both CCSVI and MS cause some reduced lung function, among many other problems.

VZV vasculopathy is caused by productive viral infection in arteries. –Wikipedia.

Only arteritis and never phlebitis? If that is the case, CCSVI is not involved with VZV. VZV might cause degenerative nerve/grey-matter problems and atrophy, but not phlebitis, apparently.
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