New study: blood flow, brain atrophy & MS

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New study: blood flow, brain atrophy & MS

Postby cheerleader » Thu Aug 21, 2014 9:02 am

The study out of NYU looks at cerebrovascular reactivity, or CVR. CVR is how the brain reacts or responds with blood flow when there is vasodilation. This function is extremely important, as neurons need adequate blood flow to provide glucose and oxygenation. Without this response of adequate cerebral bloodflow (CBF), the brain will not function properly, and neurons can potentially die.

http://archneur.jamanetwork.com/article ... id=1893478

Patients with MS had a significant decrease of cerebrovascular reactivity compared with controls. This decrease in CRV correlated to gray matter atrophy, but did not correlate with white matter lesions.

Their conclusion was that there is an impairment in the cerebrovascular pathophysiology in pwMS, and that inadequate blood flow to neurons may indeed be the cause of neurodegeneration in MS. And that this was a vascular problem, NOT a problem initiated by white matter lesions.

We know that impaired CVR is related to arterial stenosis and occlusion of the blood vessels in the neck.
http://www.hindawi.com/journals/rrp/2012/268483/

More info:
http://ccsviinms.blogspot.com/2014/08/i ... ty-in.html
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Re: New study: blood flow, brain atrophy & MS

Postby HarryZ » Thu Aug 28, 2014 7:35 am

Patients with MS had a significant decrease of cerebrovascular reactivity compared with controls. This decrease in CRV correlated to gray matter atrophy, but did not correlate with white matter lesions.



Cheer,

This info will not bode well with the white matter lesion measurements that the main MS drugs hang their hat on. Wonder how long it will be before this angle on MS gets the attention it deserves.

Harry
Last edited by HarryZ on Thu Aug 28, 2014 10:46 am, edited 1 time in total.
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Re: New study: blood flow, brain atrophy & MS

Postby Leonard » Thu Aug 28, 2014 8:06 am

Cheer,

I think that MS has many aetiologies. The Human Endogenous Retro Virus (HERV) of the W-family is central to the development of MS as well as many other immune diseases such as arthritis. Herpes simplex, Varicella Zoster (VZV) and Epstein-Barr (EBV) are members of the family. The chronic HERV infection is caused by a weakened immune system; and poor gut health and bacterial inbalance (which allows viruses and fungi to replicate or get out of control).

Chronic Cerebro Spinal Venous Insufficiency (CCSVI – blocked internal jugular veins) is specific to MS. CCSVI causes vascular damage (compromises the Blood Brain Barrier) as well as problems with the drainage/flow of the Cerebro Spinal Fluid (CSF). CCSVI links the drainage of the dural nerve system, the dural sinuses, and meningeal inflammation. It provides an explanation for meningeal inflammation and subpial cortical lesions exclusively observed in MS patients.

A third factor predisposing people is the kidney/renal system producing Asynchronous DiMethyl Arginine (ADMA), due to a late maturation of the system. ADMA is an endogenous inhibitor of all forms of Nitric Oxide synthase. The capacity to vasodilate is dependent on how much endothelial Nitric Oxide synthase we have to make Nitric Oxide. In people with MS there is a very high level of inducible Nitric Oxide synthase (iNOS) rather than endothelial (eNOS). The ADMA depletes eNOS and iNOS arises as a natural response.

In patients with MS, there is an unbridled production of EBV immune complexes in response to chronic HERV/EBV infection. These antibodies are non-working EBV infected B cells and release super oxygen. This super oxygen reacts with nitric oxide which is induced and available at high concentrations due to ADMA. The product is peroxynitrite which is by far the worst free radical nitrating the lipids (including brains). The peroxynitrite disables glyceraldehyde-3-phosphate and ADP/ATP conversion. This causes the lesions, jams the membranes/cells and causes a mitochondrial energy failure / the ion pump to fail.

The mechanisms causing disability progression and the lesions are only loosely coupled. The HERV VZV and EBV cause direct vasculopathy and inhibits OPC differentiation causing the replenishment of new dendrocytes to stall.

Autoimmunity is explained by chronic high concentration EBV immune complexes cross-coupling with epitodes of EBV remnants in transgenic cells. About 8% of cells in our body is transgenic, after about 120 million years of evolution. The immune system is normally tolerant for transgenic cells formed during the first months of foetus.

A more detailed assessment of MS can be found on the 1st page of general-discussion-f1/topic15188.html

Leo
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Re: New study: blood flow, brain atrophy & MS

Postby cervocuit » Thu Aug 28, 2014 8:36 am

Another point of view on low cerebrovascular reactivity in MS:

Impaired cerebrovascular reactivity in multiple sclerosis and its restoration with interferon beta therapy measured using breath-hold functional MRI
http://registration.akm.ch/einsicht.php ... KEN_ID=900
Conclusions. Abnormally low CVR in MS patients appeared to be restored following IFN beta treatment. As CVR is a component of neurovascular coupling relevant for preserved tissue physiology and integrity, this study suggests that altered CVR may affect brain functional responses and development of damage in MS. The effect of immunomodulation on CVR in patients suggests that altered CVR is related to inflammation and supports further investigations on the use of regional CVR as a potential early marker of therapeutic effect.
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Re: New study: blood flow, brain atrophy & MS

Postby cheerleader » Thu Aug 28, 2014 3:59 pm

Interesting presentation, cervocuit...but there's been no publication, however.

It seems that the NYU researchers knew about the hypothesis that CVR might be related to inflammation in MS, which is why they went to the trouble of showing that CVR was not correlated to white matter lesions or inflammation, but was related to gray matter atrophy in MS. In fact, there was a significant negative correlation between lesions and CVR.
And they published in a peer-reviewed neurological journal.
http://archneur.jamanetwork.com/article ... id=1893478

Results: A significant decrease of mean (SD) global gray matter CVR was found in patients with MS (3.56 [0.81]) compared with healthy controls (5.08 [1.56]; P = .001). Voxel-by-voxel analysis showed diffuse reduction of CVR in multiple regions of patients with MS. There was a significant negative correlation between gray matter CVR and lesion volume (R = 0.6, P = .004) and a significant positive correlation between global gray matter CVR and gray matter atrophy index (R = 0.5, P = .03).

Conclusions and Relevance: Our quantitative imaging findings suggest impairment in functional cerebrovascular pathophysiology, by measuring a diffuse decrease in CVR, which may be the underlying cause of neurodegeneration in MS.


Here's another earlier published paper on CVR in MS---
http://www.jscimedcentral.com/Neuroscie ... s-1051.pdf

and another one looking at cerebral hypoperfusion and CVR--
http://www.hindawi.com/journals/cpn/2012/367516/

Time to fully explore the vascular connection to MS.
http://ccsviinms.blogspot.com/2013/09/m ... perfu.html

cheer
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Re: New study: blood flow, brain atrophy & MS

Postby Kronk » Thu Aug 28, 2014 9:17 pm

Nice research as usual cheer. You have convinced me the vascular system is involved in the onset of MS. However I still cannot make the jump from stretching 2 veins in the neck to resolving blood flow to the entire CNS. I am anxiously awaiting the results from the UBC study.
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Re: New study: blood flow, brain atrophy & MS

Postby cheerleader » Thu Aug 28, 2014 9:50 pm

Never said cerebral hypoperfusion was restored by "stretching 2 veins", Kronk. Repairing venous function is only one part of the equation, just as angioplasty is not considered a "cure" for cardiovascular disease or stroke. It takes lifestyle intervention, as well. That was Dr. Cooke's message to us at Stanford.
Jeff has been following the Endothelial Health Program for 7 years, along with having venoplasty. Daily cardiovascular exercise, Swank based diet, whole foods w/plenty of phytonutrients, UV ray therapy, meditation, probiotics, etc. have allowed for a reversal of gray matter atrophy and no further MS progression. Here's the whole program:
http://ccsvi.org/index.php/helping-myse ... ial-health

Endothelial dysfunction is systemic (which was why we saw capillary fragility and petechiae on Jeff's legs--not just spots on his brain on MRI.)
The UBC study will be a part of the ongoing discovery of the connection, but certainly not the final word. It's not just venoplasty--it's a whole new life. http://ccsviinms.blogspot.com/2014/06/t ... elium.html
cheer
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Re: New study: blood flow, brain atrophy & MS

Postby Leonard » Fri Aug 29, 2014 1:58 am

you should not underestimate the viral component either, it is central to MS.
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Re: New study: blood flow, brain atrophy & MS

Postby cheerleader » Fri Aug 29, 2014 8:29 am

No underestimation here, Leonard. Viruses are known endothelial disrupters--and antivirals are part of the Endothelial Health Program. So are probiotics. Here's more on how the ebola virus destroys the vasculature, killing the host. It disrupts the endothelial layer, making it more permeable.
http://www.npr.org/blogs/goatsandsoda/2 ... -the-virus
which is why doctors are treating endothelial dysfunction in this recent ebola virus outbreak--
http://www.nytimes.com/2014/08/16/opini ... .html?_r=0

Here's more on EBV from a published paper by BNC, which I wrote about in 2011

It is quite possible that venous stasis, or slowed cerebral drainage, could be responsible for the number of viruses (such as EBV and HHV) and bacteria (such as Cpn and Lyme) that have been associated with MS-by allowing these infectious agents to pass through the blood brain barrier. Here is the Buffalo review on this topic:

The association between EBV infection and CCSVI has not yet been explored; however, it could be hypothesized that venous stasis in the superior saggital sinus due to extracranial outflow impairment could affect the drainage of bridging veins that pass through the subarachnoid space (near the meninges and EBV-infected B-cell follicles) and contribute to EBV activation. The venous stasis hypothesis in the SSS may contribute to understanding why so many different viruses and bacteria [3,111] have been linked to increased MS susceptibility risk over the last 50 years.
http://www.expert-reviews.com/doi/abs/10.1586/ern.11.117

http://ccsviinms.blogspot.com/2011/08/b ... d-ebv.html

There are dozens of endothelial disrupters. It's not one thing, have never said it was.
Once again, here's what I've been writing about for 7 years. http://ccsvi.org/index.php/helping-myse ... ial-health
The central, connecting factor is the health of the endothelial cells, throughout the 60,000 miles of blood vessels in the human body.

cheer
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Re: New study: blood flow, brain atrophy & MS

Postby Leonard » Tue Sep 02, 2014 2:03 am

Thank you cheer for your considerations. These considerations were very useful. Together we can complete the picture. I have added the endothelial dysfunction to my own assessment on the other thread, it was there already but now it is more explicit.

In the case of MS, the endothelial disrupter is the cytomegalovirus.
http://en.wikipedia.org/wiki/Cytomegalovirus

This family of herpes viruses includes the Varicella Zoster virus (VZV). This small cohort study about VZV vasculopathy seems insignificant but in reality it is groundbreaking. The vasculopathy is not only for cerebral arteries but also for the finest capillaries, the 60,000 miles of blood vessels in the human body.
http://www.ncbi.nlm.nih.gov/pubmed/24556269

As regards your other comment, I think the HERV / cytomegalovirus lies at the centre of the endothelial disruption. Bacteria such as Cpn and fungi come into the picture in a different way. Because the immune system is producing EBV immune complexes that don't work it goes on and on and on, in an unbridled manner, to produce these immune complexes. And then the immune system forgets about the rest, the IgG3 is depleted (hypo gamma globulin). And it is at this point that bacteria, fungi and perhaps other viruses get their way. And you get chronic infection, other viruses that emerge, bad bacteria and fungi that grow resulting in such things as leaky gut --> Ɛ toxin in circulation, mycoplasma, Cpn infection which may block receptors and then you get RR, even toenails fungus. This also may result in a further unbalance of gut bacteria, you get into a vicious circle with further weakening of the immune function etc.

I think the association between EBV infection and CCSVI is relatively straight forward. It is the cartilage (the meningis, tissue of the sinuses) that inflammates first; this also happens for instance in rheuma arthritis. What I found most interesting here is that the internal jugular veins (IJVs) not only relate to an impaired blood flow but that also the Cerebral Spinal Fluid drains in the IJVs. The rest of the brains is just fat, biologically seen, that is poisoned by the high concentration of peroxynitrate.
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Re: New study: blood flow, brain atrophy & MS

Postby cheerleader » Tue Sep 02, 2014 2:52 pm

Hi Leonard--
I'm not sure who you are, but I'm certainly not a doctor. I'm simply the wife of a man with MS who took research to Stanford University in 2008 and began working with researchers there to explore the vascular connection to MS.

The International Society of Neurovascular Disease (ISNVD) is the group that I've worked with, attended conferences, fund raised for, and helped to bring in new members from around the globe. I simply write about the research they are doing, but I am not a researcher myself.

Dr. Yulin Ge, one of the NYU authors of the paper I linked in the first post, is a member of the ISNVD. If you are a physician or researcher wanting to "complete the picture" of MS aetiology, I suggest you contact them. http://www.isnvd.org
best,
cheer/Joan
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Re: New study: blood flow, brain atrophy & MS

Postby Leonard » Wed Sep 03, 2014 12:36 am

thank you cheer, I will follow up.

Aside, I am not a medical doctor or researcher. I have a degree in communications engineering and worked for almost 35 years in various positions in international organisations/companies, the last one on innovation policy.

I was diagnosed with MS in 2004, obediently went to my neurologist every year, and everytime found myself with my back against the wall. This changed all of a sudden in 2009 when I learned about Zamboni, and about the social fora on the Internet.

The rest of my story you can read on the other thread. As time moved on and we learned more about the disease, my contacts with the medical establishment gradually intensified.
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