Hypoperfusion (decreased blood flow) in MS- research break-down!

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Today at 1:53pm

Before 2009 comes to a close, I'd like to share more research on the decrease of blood flow in the MS brain. There are many researchers around the globe using new MRI technology to study slowed perfusion (slow travel time of blood) in MS brains.

I would like to break down this one medical research paper for you, to show you how these researchers' findings can be linked what Dr. Zamboni has discovered- I will quote sections from the paper- and then we will discuss....

Hypoperfusion of the cerebral white matter in multiple sclerosis: possible mechanisms and pathophysiological significance
This work was supported by MS Anders (Amsterdam, The Netherlands).
Jacques De Keyser1,2, Christel Steen2, Jop P Mostert2 and Marcus W Koch2
1Department of Neurology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel,Brussels, Belgium
2Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Correspondence: Professor Dr J De Keyser, Department of Neurology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, Brussels 1090, Belgium. E-mail: jacquesdekeyser@gmail.com

Received 2 May 2008; Revised 13 June 2008; Accepted 16 June 2008; Published online 2 July 2008.

http://www.nature.com/jcbfm/journal/v28/n10/full/jcbfm200872a.html

from the abstract:
"A number of recent studies using perfusion magnetic resonance imaging in both relapsing and progressive forms of MS have shown a decreased perfusion of the NAWM, which does not appear to be secondary to axonal loss."

-this means that in normal appearing white matter in MS brains, there is a slowing of blood flow which does not appear to be caused by axonal death. Something else is causing the slowed blood flow FIRST-because it shows up before we see lesions.

"The classic teaching is that MS is a T-cell-mediated autoimmune disorder of the central nervous system. However, a number of pathophysiological observations cannot be simply explained on the basis of autoimmune mechanisms. First, the progressive (neurodegenerative) component of the disease continues despite intense immunosuppressive interventions that effectively stop inflammatory disease activity (Coles et al, 1999; Metz et al, 2007; Roccatagliata et al, 2007; Samijn et al, 2006). Second, pathologic studies have shown that some demyelinating lesions develop without a preceding inflammatory reaction (Barnett and Prineas, 2004; Gay, 2007, 2006; Guseo and Jellinger, 1975; Lucchinetti et al, 2000). Third, another intriguing finding difficult to explain by autoimmune phenomena is the finding of a diffuse cerebral white matter hypoperfusion, which is the subject of this review."

-OK. This is basically saying that the prior thought has been that MS is a t-cell mediated disease, autoimmune, blah, blah...we've all heard this. HOWEVER, the researchers wonder, how can the autoimmune hypothesis explain what we (many other researchers) are observing?
1. Even when suppressing the immune system, damage continues in the MS brain
2. Demyelinating lesions appear BEFORE inflammation
3, There is a slowing down of blood flow in cerebral white matter in MS brains

"A number of studies using single photon emission computed tomography or positron emission tomography found reduced cerebral blood flow (CBF) in the gray and white matter of patients with MS, but these findings received little attention in terms of their possible pathophysiological significance (Brooks et al, 1984; Lycke et al, 1993; Sun et al, 1998; Swank et al, 1983)."

-Whaddya know! Researchers have noticed this before, even before the new MRI technologies...see Dr. Swank's name? Their discovery received little attention...but reduced cerebral blood flow in MS has been noted before.

"Ge et al (2005) interpreted the hypoperfusion in NAWM as a vasculopathy in the context of the perivascular inflammations that occur in focal MS lesions. However, although inflammatory infiltrates in MS are typically located around small- or medium-sized veins (Adams, 1989) and in the perivascular spaces surrounding arterioles (Gay, 2006; Gay et al, 1997), microvessel thrombosis is only exceptionally being observed within these lesions (Aboul-Enein and Lassmann, 2005; Wakefield et al, 1994). A primary vascular pathology, as seen in vasculitis, would lead to regional cerebral perfusion defects rather than a generalized microvascular hemodynamic impairment as observed in MS. Furthermore, the finding that enhancing white matter lesions show increased CBF and CBV, likely caused by inflammation-mediated vasodilatation (Ge et al, 2005; Wuerfel et al, 2004), strongly argues against inflammation as the causal factor. The absence of structural (peri)vascular pathology (Aboul-Enein and Lassmann, 2005) indicates that hypoperfusion of the cerebral white matter in MS has a functional origin."

-Here are some of the papers I linked to on the other post. Ge, Wuerfel, Lassmann- they've all noticed this slowed blood flow in the MS brain. These researchers take this further, by noting that the infiltrates are located around VEINS. If MS was a primary vascular disease, like vasculitis, you'd see inflammation all over the brain...but in MS, it's just around the VEINS- and looks to be a primary injury, not secondary to inflammation. This shows that the veins are implicated in this slowed perfusion.


"Accumulating evidence indicates that there is a decreased perfusion throughout the NAWM in patients with MS. It occurs in both relapsing–remitting and primary progressive MS, strongly suggesting that it represents an integral part of the disease process. Ischemic changes might be involved in the development of a subtype of focal demyelinating lesions (type III lesions). There appears to be a relationship between reduced white matter perfusion and cognitive dysfunction in patients with MS. We provide a hypothetical framework for the reduced perfusion, implicating a key role of astrocyte dysfunction, possibly related to a deficiency in 2-adrenergic receptors resulting in an impaired siphoning and release of K+ in the perivascular spaces. The underlying pathophysiological mechanisms need to be further elucidated as it could ultimately allow us to understand and treat this complex disease better."

-The researchers spend a great deal of time in the paper hypothesizing over causes for this slowed perfusion, and finally admit that there needs to be further study. They write about research into astrocyte (glial cells in the central nervous system) disfunction, but admit they don't really know what's going on. They haven't found the specific cause for this slowed perfusion and lack of oxygen in the MS brain, and further research needs to be done. The things they can show is that MS brains have slowed blood flow, damage due to lack of oxygen that is centered around the veins in the brain, and this happens before lesions form.

So, how does this link to Dr. Zamboni's research? If deoxygenated blood cannot leave the brain in a timely matter, due to blockage and reflux of the veins that drain the brain and spine, there will be damage to the white matter (myelin) because of ischemic or hypoxic injury (lack of oxygen.) Slowed perfusion simply means, slow blood in the brain. I believe Dr. Zamboni has found the mechanical cause for what researchers around the globe have been noticing in the MS brain. More research will tell the full story.

Now, we can look up more papers on "hypoperfusion and multiple sclerosis" and see that other researchers, around the world, are noticing this too-

http://www.ajnr.org/cgi/content/abstract/28/4/767

http://jcp.bmjjournals.com/content/47/2/129.abstract

Here's a mouse study where they actually gave mice optic neuritis and white matter lesions that looked like MS (in the corpus callosum!)- they did it by closing off the carotid arteries (oxygen going in) Doctors at Stanford are now trying to do it by closing the jugular veins in mice (deoxygenated blood leaving the brain, taking too long and slowing the delivery of oxygen in)- and seeing if mice get CCSVI.

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6SYR-44D4S2Y-5&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=1151006441&_rerunOrigin=google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=70037977230e145af034db222a569e51

-OK. I've got to get cooking for our New Year's Eve Party!!!!
Happy New Year to all. In 2010, my hope is that we get reading, study the recent MS research and become educated patients and care-givers. There will be many doctors coming forward, trying to disprove Dr. Zamboni's research, and using medical phraseology they think will intimidate us. If we have a grasp on the recent research, and know the vocabulary, we can counter their arguments.

The autoimmune theory is just a theory. Until we have facts, let's keep learning together-
Joan

Jeff Shepard Just a thought, but if water becomes stagnant and developes bacteria and parasites, then improper blood flow to the brain, I would think, cause an immune response predicated on circumstance.

For example, if you have a virus and are down for the count, how many ended up in a relapse. I have everytime. Is this caused by the inability to keep the blood flowing properly out of the brain which may increased the iron? Viruses like iron.

In fact viruses are attracted to iron. Iron is needed for viruses to replicate effectively. Viruses cause an immune response and inflamation causes disability. This site, in 2000 stipulates the needs for iron as babies but is doubled edge sword when were adults with coorlation with multiple sclerosis, Alzheimer’s, and Parkinson’s. Having known that then, why is it now that we delay the trials for CCSVI?... See More

I believe the medical community is right about autoimmunity BUT, Dr Zamboni's discovery is the key to reduce this autoimmunity effect in MS.

I totally believe CCSVI is resolute with autoimmunity in the development of MS, Alzheimer's and Parkinson's. The industry is going to try to diffuse any credibility of Dr Zamboni's findings. They have much money and jobs to lose.

The thing that bothers me is that I understand these things, I'm sure the industry understands as well, but they have a fiduciary responsibility to their stock holders, being most people with 401k. (Fiduciary: An individual, corporation or association holding assets for another party, often with the legal authority and duty to make decisions regarding financial matters on behalf of the other party. ref: http://www.investorwords.com/1932/fiduciary.html)

Biogen profit up 23% as Avonex, Rituxan sell well.
http://www.marketwatch.com/story/biogen-idec-profit-up-23

Teva Reports Second Quarter 2008 Results.
http://www.tevapharm.com/pr/2008/pr_781.asp

Bayer 2008 revenue rises, profit plunges.
http://www.post-gazette.com/pg/09063/952908-28.stm

News on CCSVI

Hope and Elation/Frustration and Anger- a new CCSVI article by Dr. Ashton Embry

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Yesterday at 7:37pm

Dr. Ashton Embry found me last summer (as "Cheerleader" on This Is MS.com) after reading some of my postings regarding CCSVI online. He then wrote about CCSVI for MS Pathways and his own website and put me in touch with his fellow Canadian, Avis Favaro of CTV. We owe so much to this gentleman- as the father of a son with MS, he has funded research and sought answers- creating programs such as The Best Bet Diet. He has served as an intelligent and outspoken advocate for MS patients worldwide. Here are his latest thoughts on CCSVI from his website, direct-ms.org

Thanks, Dr. Embry-
Joan

http://www.direct-ms.org/magazines/Hope%20and%20Elation.pdf

Hope and Elation - Frustration and Anger – Fear and Loathing:
The Contrasting Emotional Responses to the Revolutionary
Discoveries in MS Made by Dr Zamboni

Dr. Ashton Embry


The beautifully crafted, CTV documentary on the astounding findings of Dr Zamboni and his team for multiple sclerosis has hit the MS community like a tidal wave and has evoked a variety of emotional responses. Most people with MS see CCSVI as a huge breakthrough for understanding and treating MS and had an initial feeling of unbridled elation that finally there was some real hope for an effective treatment on the horizon. I expect most people with MS thought “I have to get my veins checked out!”, even before the credits rolled on the Zamboni documentary.

Such a reaction is completely understandable. Dr Zamboni’s research leaves very little doubt that most people with MS have impaired venous flow from the brain and that such a problem is caused by narrowings and outright blockages in the main veins which drain the brain. To anyone with a semblance of objectivity, this is a “no drainer”. I might note that small studies in Poland and at both Stanford and the University of Buffalo in the USA have already confirmed these findings. The University of Buffalo is now doing a very large study to add further confirmation. I would be willing to bet the farm that this study will validate Dr Zamboni’s findings and, most importantly, it will silence the vocal skeptics, many of whom are neurologists with a blatant conflict of interest regarding the emergence of a potentially effective, non-drug treatment.

I have noticed from discussions with numerous persons with MS over the past few weeks that the initial feelings of excitement and hope have been replaced in many cases by anger and frustration. This has come about because everyone is finding it impossible to get an MRV to determine if they indeed have venous blockages. In Calgary, one person I was speaking with called every private imaging clinic and got no where. The receptionist at each clinic simply read a prepared response they had gotten from Alberta Health that there is not enough evidence to warrant such a scan. I quote from a November 26th email from the manager of one clinic “Until we get further instruction … we don't feel that ethically we can institute these scans for patients”. Always nice to know the Alberta government is out there making sure persons with MS do not find out if they have a serious venous problem or not.

I have spoken to a few dozen persons with MS and each one expressed their burning desire to find out if CCSVI affects them and if so, how badly. And each one was very angry and frustrated that there was no way they could get such an important test done. The fact that the government substantially contributed to the problem only made them angrier.

When it comes to fear and loathing, I expect these feelings are being harboured by other constituencies of the MS community, namely the MS clinicians, researchers, drug companies and charities. Why would such pillars of medicine fear and hate CCSVI? Regarding the clinicians, I have no doubt that they quickly realized that, if relief of CCSVI is an effective treatment, especially for the newly diagnosed, then they would essentially be cut out of the action when it comes to treating MS patients. Once a person was diagnosed with MS they would be immediately be referred to a vascular specialist who would then oversee the person’s treatments. It would be “diagnose and adios” for the neurologists, a somewhat ironic development given that is how the neurologists used to treat MS patients before the advent of MS drugs in the mid-90s .

As far as the MS researchers go, I can definitely empathize with them. I have been involved in research for over 40 years and I know, if someone suddenly demonstrated that I had spent the last 40 years barking up the wrong tree, I would have a variety ofintense, negative feelings. One thing that has never been mentioned is how the Zamboni results demonstrate that the EAE animal model, which is widely used in MS research and upon which 10s of millions of dollars are spent every year, is clearly not suitable and is almost worthless. The mice do not develop CCSVI and thus the EAE model is no betterthan an animal model in which the mice developed CCSVI but no CNS lesions. A viableanimal model for MS needs to exhibit both phenomena – end of story. Such a realization will cause great gnashing of teeth in the wide world of MS research.

It is also not a stretch to predict that fear and loathing in the MS research community will
turn to anger and I hope Dr Zamboni is prepared for some blistering attacks on both his work and his character. Hell hath no fury like a researcher proven wrong or disenfranchised. Finally, I won’t belabour the fears and anger of both the clinicians and the researchers regarding the potential loss of all that drug company largesse and research money which has been a bonanza over the past 15 years.

That brings us to the drug companies that supply the drugs that currently are used to treat
MS or are in development. I have no doubt these companies must be having hand- wringing meetings these days to discuss the threat of a potentially effective, non-drug treatment for MS. The boardrooms must reek of fear and loathing when the obvious implications of the Zamboni discoveries are discussed. The bottom line is that there are tens and possibly hundreds of billions of dollars at stake in the foreseeable future and the drug companies are not going to let that kind of serious cash simply disappear without a fight. It is impossible to predict how the companies will deal with this real threat to their bottom lines and stock prices but you know it is not going to be pretty.

Finally I suspect there is a lot of fear and loathing going on at the national MS societies
in the countries with high rates of MS (e.g. Canada). For the MS Society of Canada this has been a public relations disaster which potentially will translate into a loss of revenue. The most obvious, embarrassing aspect of this fiasco is the fact that MSSOC wasn’t even aware of the Zamboni research until mid October when they put up on their website afew, pathetic paragraphs on CCSVI that were cribbed from NMSS. They had absolutely no plans to fund any research on CCSVI until the CTV documentary put a gun to their head and they then hastily cobbled together a press release (in which Dr Zamboni’s name was mis-spelt) and issued a call for CCSVI research proposals.

The big question is why, with their blue-ribbon scientific advisory board, did MSSOC have no clue about CCSVI when papers on the subject began appearing in 2006 and major contributions were publicly available in late 2008 and early 2009. Were all their scientific advisors asleep at the switch? Assuming these renowned researchers read the scientific literature, do they have they the ability to recognize a watershed contribution when it crosses their desk? The fact CCSVI went unnoticed by MSSOC for more than a year is cause for serious concern about the competency of the organization in terms of providing reliable and timely scientific information to their members. What other important information is currently out there going unnoticed by MSSOC and its scientific advisors?

To sum up, Dr Zamboni’s amazing and groundbreaking discoveries have induced a wide variety of emotions in the different factions of the MS community. Such emotions are going to make it even harder for his findings to be properly tested and, if proven to be correct, to be incorporated into clinical practice. Regardless, it is important to realize that such strong emotions exist and to be cognizant of the different and somewhat antagonistic views and goals of the two groups that comprise the MS family – those that live with MS and those that live off MS.